How to Build Clinical Reasoning Skills in Medical School (Using What You Already Know)
Master clinical reasoning in medical school by learning how to apply your book knowledge to real cases and develop real-world diagnostic thinking...
Struggling with differential diagnosis? This clinical student blog covers clinical reasoning tips, common mistakes, and strategies for accurate diagnosis.
--
--
Building a strong differential diagnosis is a critical skill for medical, PA and NP students learning clinical reasoning. Whether you’re on clinical rotations or preparing for board exams, knowing how to systematically approach symptoms, rule out conditions, and prioritize potential diagnoses is essential for patient care.
In this blog, we’ll break down how to develop a differential diagnosis, key clinical reasoning techniques, and common mistakes to avoid. By mastering this diagnostic process, you’ll improve your diagnostic accuracy, enhance your problem-solving skills, and build confidence in your clinical decision-making.
This blog is written by a medical student, but building a differential diagnosis can apply to all clinical students!
--
Congratulations! You’ve made it through your didactics, which were packed with lectures, textbooks, and plenty of Sketchy.
Now, as a brand-new clinical student who’s hitting rotations for the first time, you’re stepping into the hospital, where you’ll be expected to apply everything you’ve learned to real patients. But here’s the challenge: real patients don’t present like textbook cases.
As an aside, the point above is one reason why we do rigorous clinical training in school. Your clinical rotations will prepare you to think critically, analyze, and put into practice your extensive “book knowledge.”
But, while the textbook case is a slam dunk, real-life cases require you to consider alternative diagnoses and refine your clinical reasoning skills in medicine. And, even if the diagnosis ends up being exactly what you expected, humans are unique and like to present the same condition in a thousand different ways.
Obviously exaggerating but the point being, it’s one thing to learn to take an H&P, and it's another to generate a differential diagnosis, but it's all about building your clinical acumen to, for lack of a better word, sense (or commonly joked as “smell”) when something is different.
Now, back to rotations—you’re doing your first rotation and you just beautifully presented a patient’s H&P to your attending. Suddenly, you're asked, "What’s on your differential?" and your mind floods with every disease you’ve ever read about.
Clinical reasoning involves applying the knowledge and skills to collect, integrate, and do something with the information (such as the medical history, labs, or imaging tests) in an appropriate manner to apply interventions (e.g., medications), solve clinical problems (e.g., why is this person acutely confused?), and ultimately influence patient outcomes1.
This blog will walk you through the essential strategies to transition from book knowledge to clinical reasoning skills for medical, PA, and NP students.
Your first instinct might be to recall everything you watched in Sketchy or read in First Aid, but clinical reasoning skills in medicine isn’t just about memorizing facts—it’s about thinking like a clinician. There are two main ways physicians approach problems:
Pattern Recognition | This is fast, experience-based decision-making. For example, an elderly smoker with sudden, severe dyspnea? Probably a COPD exacerbation. |
Analytic Reasoning | This is the structured, step-by-step method of generating a differential diagnosis when you’re uncertain. You’ll be using this a lot in the beginning and this is primarily what we will focus on. |
As a new clinical student, your focus should be on developing structured reasoning habits while learning to recognize common patterns over time. Beware of these common pitfalls:
Want to learn more about incorporating your book learning with clinical reasoning: check out this blog.
When coming up with differential diagnoses, avoid the "Oh no, I can’t think of anything!" moment by using structured tools. One classic framework, and the one I learned in school, is the VINDICATE mnemonic, which ensures you don’t overlook key disease categories:
Let’s apply this to a sample case. For example, the causes of shortness of breath are myriad, but using VINDICATE we get:
Now that you’ve worked through what could be going on, it’s time to narrow it down. Because, as much as it’s rewarding to find a “zebra” or diagnose something very rare, it’s simply not common. One of my go-to phrases is “common things are common.”
Traditionally on rounds your resident or attending or preceptor will expect you to mention at least three potential diagnoses. Here is how I chose to structure that conversation:
Let’s practice again by considering the following case: A 47-year-old male presents with severe epigastric pain and nausea.
There is another popular structure for considering your differentials called “Worst First.” As someone going into Emergency Medicine, this is a method I’m accustomed to. You still want to have a most likely condition, a few “this is possible” conditions, but include one to two life-threatening conditions that you absolutely cannot miss.
Simply put, it’s the same list you generated, but when presenting, you mention the scary stuff first. Your attending or preceptor will know that you’re considering these can’t miss diagnoses, while also recognizing that there is likely something else going on that won’t kill the patient.
Alright, so now we know what clinical reasoning is, how to use the VINDICATE mnemonic, and how to structure your differential diagnosis in a presentation. But, before we can apply these mnemonics and frameworks, we need data.
Data comes in the form of the history, physical, labs, and imaging. To me, clinical reasoning falls along this timeline: Gather a history (asking questions to rule-in & rule-out conditions), perform a thorough physical exam, decide what testing or imaging you would use (or not at all!), generate a differential diagnosis based on the chief concern, and then integrate these data points to narrow your differential like the test results. Let’s walk through it step-by-step.
Master patient case presentations with this complete guide. Learn how to structure and deliver concise, effective patient presentations for each clinical rotation.
The best diagnosticians aren’t the ones who order the most tests—they’re the ones who ask the right questions. When gathering a history, think in terms of:
After asking open-ended questions, such as "Tell me about your chest pain," try targeted questions with a purpose:
It can be helpful to “prime” patients by giving them a glimpse into your decision-making. For example, “I’m going to ask you some specific questions that might seem all over the place, but they help guide me to what is most likely going on.”
As with the targeted questions you ask during a history, your exam should be hypothesis-driven—what findings will help confirm or refute your suspected differentials?
For example, for our shortness of breath patient from earlier:
Before you order a test, ask yourself:
Laboratory tests or imaging can provide an insight into the inside of the body as well as identify things that patients cannot put into words. It’s hard for a patient to say, “I feel hypokalemic.” But, when their potassium comes back quite low, that could be a reason for why they’re feeling so tired.
Check out this blog on 10 Lab Tests to Know as a Clinical Student. Read about common labs you should know on your clinical rotations.
One place where students and those less comfortable with their H&P skills get caught up is what’s called “shotgunning” tests—ordering a broad panel of tests without a clear diagnostic strategy. Consider, once again, our shortness of breath patient. If they are middle-aged, on oral contraceptives, had cancer, just got off a trans-atlantic flight, and have a bedside POCUS concerning for DVT, then PE should be at the top of your differential diagnosis (and at the top of worst-first too!).
Do you need a D-dimer in this patient? Or can you skip straight to imaging? Using the Wells’ Criteria for Pulmonary Embolism, you should skip the D-dimer and proceed directly to a CT scan. Don’t forget that every test you order involves (1) many hospital staff and resources, (2) potential pain for the patient, and (3) costs incurred that the patient may have to bear!
All of the above information is important, but practice makes perfect. Ideally you can apply these methods on real patients in the hospital or clinic. Some active-learning tips include:
One of the best tools you can use to practice is DDx by Sketchy. Access over 60+ interactive patient cases and weekly diagnosis games, refine your diagnostic reasoning skills, and get real-time personalized feedback. Each case links back to Sketchy lessons to help reinforce your learning. Curious how to study for clinical with Sketchy - read this blog!
Now that we’ve covered how to build a differential diagnosis and why it matters, we want to make the process a bit easier. While generating a differential from scratch each time is a valuable cognitive exercise, it’s also helpful to recognize that certain patient concerns are commonly associated with specific signs, symptoms, and diagnoses. These patterns are worth committing to memory.
The following lists are organized by how frequently each chief complaint presents in two different settings: the emergency department and the primary care clinic. Use them as a reference—and as a foundation for building strong differentials for your patients.
# |
Chief Complaint |
Associated Signs/Symptoms |
Differential Diagnoses |
1 |
Abdominal Pain |
Nausea, vomiting, fever, bloating, rebound/guarding, altered bowel habits |
|
2 |
Chest Pain |
Dyspnea, diaphoresis, palpitations, nausea, radiation to arm/jaw |
|
3 |
Shortness of Breath |
Cough, wheezing, accessory muscle use, cyanosis, anxiety |
|
4 |
Fever |
Chills, myalgias, malaise, sweats, tachycardia |
|
5 |
Cough |
Fever, sputum, dyspnea, wheeze, chest tightness |
|
6 |
Headache |
Photophobia, nausea, aura, neck stiffness, focal deficits |
|
7 |
Back Pain |
Radiculopathy, weakness, urinary retention/ incontinence |
|
8 |
Trauma/Injury |
Swelling, deformity, bleeding, ecchymosis, tenderness |
|
9 |
Dizziness/ Syncope |
Lightheadedness, palpitations, nausea, diaphoresis |
|
10 |
Vomiting/ Nausea |
Dehydration, abdominal pain, fever, headache |
|
# |
Chief Complaint |
Associated Signs and Symptoms |
Differential Diagnoses |
1 |
Cough |
Nasal congestion, sore throat, mucus drainage, fever, wheezing |
|
2 |
High blood pressure (hypertension) follow-up |
Often no symptoms; may include headache or vision changes in severe cases |
|
3 |
Routine check-up |
Typically no symptoms; visit includes screenings, vaccinations, and wellness review |
|
4 |
Lower back pain |
Muscle spasms, reduced range of motion, pain that travels down a leg |
|
5 |
Fatigue |
Difficulty sleeping, weight change, low energy, lack of motivation |
|
6 |
Headache |
Tension in the neck or scalp, changes in vision, nausea or vomiting |
|
7 |
Joint pain |
Stiffness, swelling, difficulty moving the joint, pain with activity |
|
8 |
Abdominal pain |
Bloating, changes in bowel movements, nausea, pain related to meals |
|
9 |
Symptoms of depression or anxiety |
Difficulty sleeping, poor concentration, restlessness, worry, sadness |
|
10 |
Skin concerns |
Itching, redness, scaly patches, discharge, pain or sensitivity |
|
Developing clinical reasoning takes time, but every patient you see will sharpen your skills. As a clinical student, your goal isn’t to be perfect—it’s to think systematically, ask the right questions, and learn from every case.
1 Delavari S, Barzkar F, M. J. P. Rikers R, Pourahmadi M, Soltani Arabshahi SK, Keshtkar A, et al. (2024) Teaching and learning clinical reasoning skill in undergraduate medical students: A scoping review. PLoS ONE 19(10): e0309606. https://doi.org/10.1371/journal.pone.0309606
Citations for Emergency Department (ED)
Centers for Disease Control and Prevention. National Hospital Ambulatory Medical Care Survey: 2021 Emergency Department Summary Tables. National Center for Health Statistics. Published 2023. Accessed May 14, 2025. https://www.cdc.gov/nchs/data/nhamcs/web_tables/2021-nhamcs-ed-web-tables-508.pdfCDC+1CDC+1
Kocher KE, Meurer WJ, Fazel R, Scott PA, Krumholz HM, Nallamothu BK. National Trends in Use of Computed Tomography in the Emergency Department. Ann Emerg Med. 2011;58(5):452-462.e3. doi:10.1016/j.annemergmed.2011.03.033
Travers DA, Haas SW, Holder D, Waller AE. Classification of Emergency Department Chief Complaints Into 7 Presenting Problem Categories: An Empirical Analysis. Ann Emerg Med. 2005;46(5):445-455. doi:10.1016/j.annemergmed.2005.01.016
Citations for Primary Care Physician (PCP)
Centers for Disease Control and Prevention. National Ambulatory Medical Care Survey: 2019 National Summary Tables. National Center for Health Statistics. Published 2021. Accessed May 14, 2025. https://www.cdc.gov/nchs/data/ahcd/namcs_summary/2019-namcs-web-tables-508.pdfCDC+1CDC+1
Lucey CR, Wilder J, Kroenke K, Lucas C, Marple R. Concerns and Expectations in Patients Presenting With Physical Complaints. Arch Intern Med. 1997;157(13):1482-1488. doi:10.1001/archinte.1997.00440340122012
Schwartz MD, Lowe CJ, Collins BT. Burden of Difficult Encounters in Primary Care: Data From the Minimizing Error, Maximizing Outcome Study. Arch Intern Med. 2007;167(8):825-830. doi:10.1001/archinte.167.8.825
Master clinical reasoning in medical school by learning how to apply your book knowledge to real cases and develop real-world diagnostic thinking...
Prepare for clinical rotations with these 10 essential lab tests every medical student should know. Master key tests and improve your patient care...
Discover what to expect on your family medicine rotation—get tips, key topics to review, and learn who to lean on for support during your clinicals.
Subscribe to our mailing list and get exclusive studying tips, connect with our community, get first dibs on special offers and content updates.