Purpose To compare skills acquired by undergraduate nursing students enrolled in a medical‐surgical course. To compare skills demonstrated by students with no previous clinical practice (undergraduates) and nurses with clinical experience enrolled in continuing professional education (CPE). Design In a nonrandomized clinical trial, 101 undergraduates enrolled in the “Adult Patients 1” course were assigned to the traditional lecture and discussion (n = 66) or lecture and discussion plus case‐based learning (n = 35) arm of the study; 59 CPE nurses constituted a comparison group to assess the effects of previous clinical experience on learning outcomes. Methods Scores on an objective structured clinical examination (OSCE), using a human patient simulator and cases validated by the National League for Nursing, were compared for the undergraduate control and intervention groups, and for CPE nurses (Student's t test). Findings Controls scored lower than the intervention group on patient assessment (6.3 ± 2.3 vs 7.5 ± 1.4, p = .04, mean difference, ‐1.2 95% confidence interval (CI) ‐2.4 to ‐0.03) but the intervention group did not differ from CPE nurses (7.5 ± 1.4 vs 8.8 ± 1.5, p = .06, mean difference, ‐1.3 95% CI ‐2.6 to 0.04). The CPE nurses committed more “rules‐based errors” than did undergraduates, specifically patient identifications (77.2% vs 55%, p = .7) and checking allergies before administering medication (68.2% vs 60%, p = .1). Conclusions The intervention group developed better patient assessment skills than the control group. Case‐based learning helps to standardize the process, which can contribute to quality and consistency in practice: It is essential to correctly identify a problem in order to treat it. Clinical experience of CPE nurses was not associated with better adherence to safety protocols. Clinical Relevance Case‐based learning improves the patient assessment skills of undergraduate nursing students, thereby preparing them for clinical practice.