ABSTRACT: OBJECTIVE:Fostering clinical reasoning is a mainstay of medical education. Based on the clinicopathological conferences, we propose a case-based peer teaching approach called clinical case discussions (CCDs) to promote the respective skills in medical students. This study compares the effectiveness of different CCD formats with varying degrees of social interaction in fostering clinical reasoning. DESIGN, SETTING, PARTICIPANTS:A single-centre randomised controlled trial with a parallel design was conducted at a German university. Study participants (N=106) were stratified and tested regarding their clinical reasoning skills right after CCD participation and 2 weeks later. INTERVENTION:Participants worked within a live discussion group (Live-CCD), a group watching recordings of the live discussions (Video-CCD) or a group working with printed cases (Paper-Cases). The presentation of case information followed an admission-discussion-summary sequence. PRIMARY AND SECONDARY OUTCOME MEASURES:Clinical reasoning skills were measured with a knowledge application test addressing the students' conceptual, strategic and conditional knowledge. Additionally, subjective learning outcomes were assessed. RESULTS:With respect to learning outcomes, the Live-CCD group displayed the best results, followed by Video-CCD and Paper-Cases, F(2,87)=27.07, p<0.001, partial η2=0.384. No difference was found between Live-CCD and Video-CCD groups in the delayed post-test; however, both outperformed the Paper-Cases group, F(2,87)=30.91, p<0.001, partial η2=0.415. Regarding subjective learning outcomes, the Live-CCD received significantly better ratings than the other formats, F(2,85)=13.16, p<0.001, partial η2=0.236. CONCLUSIONS:This study demonstrates that the CCD approach is an effective and sustainable clinical reasoning teaching resource for medical students. Subjective learning outcomes underline the importance of learner (inter)activity in the acquisition of clinical reasoning skills in the context of case-based learning. Higher efficacy of more interactive formats can be attributed to positive effects of collaborative learning. Future research should investigate how the Live-CCD format can further be improved and how video-based CCDs can be enhanced through instructional support.