BACKGROUND: The COVID-19 pandemic caused a major disruption in the health care sector with increased workload and the need for new staff to assist with screening and vaccination tasks. Within this context, teaching medical students to perform intramuscular injections and nasal swabs could help address workforce needs. Although several recent studies discuss medical students' role and integration in clinical activities during the pandemic, knowledge gaps exist concerning their role and potential benefit in designing and leading teaching activities during this period. OBJECTIVE: The aim of our study was to prospectively assess the impact in terms of confidence, cognitive knowledge, and perceived satisfaction of a student-teacher-designed educational activity consisting of nasopharyngeal swabs and intramuscular injections for the training of second-year medical students in the Faculty of Medicine, University of Geneva, Switzerland. METHODS: This was a mixed methods pre-post surveys and satisfaction survey study. Activities were designed using evidence-based teaching methodologies based on the SMART (specific, measurable, achievable, realistic, and timely) criteria. All second-year medical students who did not participate in the activity's old format were recruited unless they explicitly stated that they wanted to opt out. Pre-post activity surveys were designed to assess perception of confidence and cognitive knowledge. An additional survey was designed to assess satisfaction in the mentioned activities. Instructional design was blended with a presession e-learning activity and a 2-hour practice session with simulators. RESULTS: Between December 13, 2021, and January 25, 2022, a total of 108 second-year medical students were recruited; 82 (75.9%) students participated in the preactivity survey and 73 (67.6%) in the postactivity survey. Students' confidence in performing intramuscular injections and nasal swabs significantly increased on a 5-point Likert scale for both procedures-from 3.31 (SD 1.23) and 3.59 (SD 1.13) before the activity to 4.45 (SD 0.62) and 4.32 (SD 0.76) after the activity (P<.001), respectively. Perceptions of cognitive knowledge acquisition also significantly increased for both activities. For the nasopharyngeal swab, knowledge acquisition concerning indications increased from 2.7 (SD 1.24) to 4.15 (SD 0.83), and for the intramuscular injection, knowledge acquisition concerning indications increased from 2.64 (SD 1.1) to 4.34 (SD 0.65) (P<.001). Knowledge of contraindications for both activities increased from 2.43 (SD 1.1) to 3.71 (SD 1.12) and from 2.49 (SD 1.13) to 4.19 (SD 0.63), respectively (P<.001). High satisfaction rates were reported for both activities. CONCLUSIONS: Student-teacher-based blended activities for training novice medical students in commonly performed procedural skills seem effective for increasing their confidence and cognitive knowledge and should be further integrated within a medical school curriculum. Blended learning instructional design increases students' satisfaction about clinical competency activities. Future research should elucidate the impact of student-teacher-designed and student-teacher-led educational activities.