A meta-analysis was performed to assess the Effect Size (ES) from randomized studies comparing the effect of educational interventions in which Virtual patients (VPs) were used either as an alternative method or additive to usual curriculum versus interventions based on more traditional methods. Meta-analysis was designed, conducted and reported according to QUORUM statement on quality of reporting of meta-analyses. Twelve randomized controlled studies were retrieved, assessing a total of 25 different outcomes. Under a random-effect model, meta-analysis showed a clear positive pooled overall effect for VPs compared to other educational methods (Odds Ratio: 2.39; 95% C.I. 1.48 [divided by] 3.84). A positive effect has been documented both when VPs have been used as an additive resource (O.R.: 2.55; C.I. 1.36 [divided by] 4.79) and when they have been compared as an alternative to a more traditional method (O.R.: 2.19; 1.06 [divided by] 4.52). When grouped for type of outcome, the pooled ES for studies addressing communication skills and ethical reasoning was lower than for clinical reasoning outcome. There is evidence that VPs are effective but further research is needed to clarify which is their best possible integration in curricula and their value and cost/benefit ratio with respect to other active learning methods. (Contains 3 tables and 3 figures.)