The primary aim of this study was to determine whether levels of student engagement, higher order skill proficiency, and knowledge acquisition demonstrated by medical students would differ when completing the same course in three diverse learning environments. Following Institutional Review Board approval, 56 first-year medical students, registered at the same medical school but attending class at three different campus centers, were enrolled in the study. All participants were completing a medical physiology course that utilized the same learning objectives but relied on different faculty incorporating diverse methodologies (percentage of class devoted to active learning strategies), course format (6-wk block vs. 17-wk semester), and student attendance. Students completed a validated survey of student engagement (SSE), a proctored online problem-based assessment of higher order skill proficiency [Collegiate Learning Assessment (CLA); http://cae.org], and the National Board of Medical Examiners (NBME) Physiology subject exam. In this limited sample, results indicate no significant differences between campus sites for any of the variables assessed. Levels of engagement were lower than expected compared with published values for graduate students. Higher order skill proficiency assessed by CLA was significantly higher than values reported for college seniors nationally. Surprisingly, SSE offered no prediction of performance on CLA or NBME, as there were no significant correlations between variables. These data indicate that, although first-year medical students may not perceive themselves as highly engaged, they are adept in using higher order skills and excel in meeting course learning objectives, regardless of learning environment.