Retrieval practice improves long-term retention. Use of interactive retrieval practice in large group, in-person and online live classes, in combination with outside resources, is unreported for medical physiology classes. The primary study purpose was to compare student cohorts' performance with or without retrieval practice in renal physiology classes, relative to the national average on customized national examinations in renal physiology, non-physiology, and all questions. The secondary purpose was to examine the students' educational experience. For the primary purpose, we used a non-equivalent group, post-test only design. For the secondary purpose, we used cross-sectional and qualitative designs. We analyzed examination results of 684 students in four academic years. For renal physiology questions, students performed significantly better in years with retrieval practice compared to years without it (P < 0.001). There was no change in non-physiology scores over the four years. Performance in all questions, too, significantly improved (P < 0.001). A large majority (86%) of students indicated retrieval practice helped them learn renal physiology. Student ratings of quality in online classes, which featured interactive retrieval practice, were higher than that of in-person classes (P < 0.001). Qualitative analysis revealed students found interactive retrieval practice, scaffolding, outside resources, and the instructor's teaching style helpful. Educators in medical physiology classes can use our findings to implement interactive retrieval practice.