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Objectives: Active learning techniques help with motivation, involvement, and retention during didactics. There are few studies comparing different active learning methods, and these have yielded mixed results. The objective of this study was to compare the effect of two active learning methods-small-group discussion and audience response system (ARS)-on immediate-and long-term knowledge gain.Methods: This was a prospective experimental study of emergency medicine (EM) subinterns and residents.Participants were randomized into two groups, and baseline knowledge was assessed with a multiple-choice pretest. Didactic sessions on salicylate toxicity and ocular trauma were given to both groups utilizing either smallgroup discussion or ARS. A crossover design was utilized to ensure that both groups received instruction by each method. A multiple-choice posttest was administered following the didactics and again 2 months later. Preand posttests were identical. All test items were written by an academic faculty member with advanced training in medical education and item writing and were based on the goals and objectives of the session. Test items were piloted with a reference group of learners. Didactic instructors were blinded to test items. Data were analyzed using a linear mixed-effects model.Results: Thirty-eight subinterns and residents participated in the study. Both instructional methods showed immediate-and long-term knowledge gain. The linear mixed-effects model did not demonstrate any significant difference between instructional methods on immediate knowledge gain (mean difference = 0.18, p = 0.62, 95% confidence interval [CI] = À0.52 to 0.88) or long-term knowledge gain (mean difference = À0.42, p = 0.36, 95% CI = À1.32 to 0.47). Conclusion:In this small study, there was no significant difference between instructional methods on immediate-and long-term knowledge gain in EM subinterns and residents.