Introduction. A “virtual patient” is defined as a computer program which simulates real patients’ cases. The aim of this study was to determine whether the inclusion of virtual patients affects the level of factual knowledge of family medicine students at the undergraduate level. Methods. This was a case-controlled prospective study. The students were randomly divided into experimental (EG: N=51) and control (CG: N=48) groups. The students in the EG were asked to practice diagnosis using virtual patients instead of the paper-based clinical cases which were solved by the students in the CG. The main observed variable in the study was knowledge of family medicine, determined by 50 multiple choice questions (MCQs) about knowledge of family medicine. Results. There were no statistically significant differences in the groups’ initial knowledge. At the final assessment of knowledge, there were no statistically significant differences between the groups, but there was a statistically significant difference between their initial and final knowledge. Conclusions. The study showed that adding virtual patient cases to the curriculum, instead of paper clinical cases, did not affect the level of factual knowledge about family medicine. Virtual patients can be used, but a significant educational outcome is not expected.