This meta-analysis has two aims: (a) to address the main effects of problem based learning on two categories of outcomes: knowledge and skills; and (b) to address potential moderators of the effect of problem based learning. We selected 43 articles that met the criteria for inclusion: empirical studies on problem based learning in tertiary education conducted in real-life classrooms. The review reveals that there is a robust positive effect from PBL on the skills of students. This is shown by the vote count, as well as by the combined effect size. Also no single study reported negative effects. A tendency to negative results is discerned when considering the effect of PBL on the knowledge of students. The combined effect size is significantly negative. However, this result is strongly influenced by two studies and the vote count does not reach a significant level. It is concluded that the combined effect size for the effect on knowledge is non-robust. As possible moderators of PBL effects, methodological factors, expertise-level of students, retention period and type of assessment method were investigated. This moderator analysis shows that both for knowledge- and skills-related outcomes the expertise-level of the student is associated with the variation in effect sizes. Nevertheless, the results for skills give a consistent positive picture. For knowledge-related outcomes the results suggest that the differences encountered in the first and the second year disappear later on. A last remarkable finding related to the retention period is that students in PBL gained slightly less knowledge, but remember more of the acquired knowledge.