Objective: To compare simulator-based teaching with traditional instruction among clinical medical students. Methods: Randomized controlled trial with written pre-post testing. Third-year medical students (n = 38) received either a myocardial infarction (MI) simulation followed by a reactive airways disease (RAD) lecture, or a RAD simulation followed by an MI lecture. Results: Mean pre-post test score improvement was seen across teaching modalities (overall change score [simulation] = 8.8 [95% CI = 2.3–15.3], pretest [62.7]; change score [lecture] = 11.3 [95% CI = 5.7–16.9], pretest [59.7]). However, no significant differences were observed between simulator-based teaching and lecture, in either subject domain. Conclusions: After a single instructional session for clinical medical students, differences between simulator-based teaching and lecture could not be established by the written test protocols used in this pilot. Future studies should consider the effects of iterative exposure assessed by clinical performance measures across multiple centers.