Objective. To compare the impact of 2 different teaching and learning methods on student mastery of learning objectives in a pharmacotherapy module in the large classroom setting. Design. Two teaching and learning methods were implemented and compared in a required pharmacotherapy module for 2 years. The first year, multiple interactive mini-cases with inclass individual assessment and an abbreviated lecture were used to teach osteoarthritis; a traditional lecture with 1 inclass case discussion was used to teach gout. In the second year, the same topics were used but the methods were flipped. Student performance on pre/post individual readiness assessment tests (iRATs), case questions, and subsequent examinations were compared each year by the teaching and learning method and then between years by topic for each method. Students also voluntarily completed a 20-item evaluation of the teaching and learning methods. Assessment. Postpresentation iRATs were significantly higher than prepresentation iRATs for each topic each year with the interactive mini-cases; there was no significant difference in iRATs before and after traditional lecture. For osteoarthritis, postpresentation iRATs after interactive mini-cases in year 1 were significantly higher than postpresentation iRATs after traditional lecture in year 2; the difference in iRATs for gout per learning method was not significant. The difference between examination performance for osteoarthritis and gout was not significant when the teaching and learning methods were compared. On the student evaluations, 2 items were significant both years when answers were compared by teaching and learning method. Each year, students ranked their class participation higher with interactive cases than with traditional lecture, but both years they reported enjoying the traditional lecture format more. Conclusion. Multiple interactive mini-cases with an abbreviated lecture improved immediate mastery of learning objectives compared to a traditional lecture format, regardless of therapeutic topic, but did not improve student performance on subsequent examinations.