Background: Despite the nearly universal practice of using standardized patients in introduction to clinical medicine (ICM) courses, no studies have compared the performance of students trained with standardized patients to that of those trained with hospitalized patients with regard to short- and long-term educational outcomes. Purpose: To examine the differential effect of the use of standardized patients in a simulation center versus the use of hospitalized patients in affiliated teaching hospitals for teaching history-taking and physical examination skills. Methods: This was a nonrandomized cohort study based on self-selection involving students from 2 academic years enrolled in an ICM course who received the final block of their ICM instruction with either standardized patients in the simulation center or hospitalized patients in affiliated hospitals. The primary, end-of-ICM (preclerkship)-outcome variables (k = 10) were data from a final observed history and physical examination, an observed structured clinical examination, a National Board of Medical Examiners subject examination for clinical medicine, and ICM preceptor evaluations. Secondary, postclerkship outcome variables (k = 5) included internal medicine clerkship scores, teacher ratings from the clerkship, and examination scores from end-of-clerkship tests. The statistical significance was set at p < .05. Results: No statistical differences were found between the means of the 2 groups in any of the primary or secondary outcome variables; there was significant power. Conclusions: The use of standardized patients in a simulated setting compared to the use of hospitalized patients in affiliated teaching hospitals is not a disadvantage in the education of students in ICM courses.