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The Studentische Poliklinik is Germany's first student-run free clinic. Prior to fulfilling clinical obligations there, students must complete an extensive peer-assisted learning program (PAL). Due to capacity constraints, a web-based learning program involving virtual patients has been launched. The aim of this study was to evaluate and compare the effectiveness of Virtual Patient Learning (VPL) vs. PAL in the acquisition of basic medical knowledge and skills. Forty undergraduate medical students (m=9; f=31) in their third year were randomly assigned to either the PAL (n=20), or VPL (n=20). Short-term (after each seminar) and long-term learning retention (after completion of the electives) was measured using a validated theoretical test. Objective structured clinical examinations (OSCE) were used to assess practical knowledge. Additionally, the course itself was evaluated. Differences in theoretical knowledge between students in the PAL and VPL existed over the short term (VPL median = 100%; PAL median = 80; p = 0.006), but not over the long term (VPL = 94.17; PAL = 95.62 %; p = 0.617). An assessment of practical skills showed no differences in OSCE scores between the two different groups (VPL = 79.30 %; PAL = 80.26 %; p = 0.141). Students assessed their learning experience and the comprehensibility of seminars as either "very good" or "good". Basic medical knowledge and skills can be taught as effectively using VPL as PAL. Given the cost-effectiveness, high reproducibility and freedom of time and place, VPL should be performed more often when teaching family medicine in student-run free clinics. Ultimately, this may result in enhanced treatment quality and patient satisfaction.