PURPOSE: Clinical empathy is a necessary trait to provide effective patient care, despite differences in how it is defined and constructed. The aim of this study was to examine whether empathy interventions in medical students are effective and how confounding factors potentially moderate this effect. METHOD: The authors performed a systematic review and meta-analysis. They searched the literature published between 1948 and 2018 for randomized controlled trials that examined empathy interventions in medical students. The search (database searching, citation tracking, hand-searching relevant journals) yielded 380 studies, which they culled to 16 that met the inclusion criteria. For the meta-analysis, they used a random effects model to produce a pooled estimate of the standardized mean difference (SMD), then completed subgroup analyses. RESULTS: The authors found evidence of the possibility of response and reporting bias. The pooled SMD was 0.68 (95% confidence interval 0.43, 0.93), indicating a moderately positive effect of students developing empathy after an intervention compared with those in the control groups. There was no evidence of publication bias, but heterogeneity was significantly high (I = 88.5%, P < .01). Subgroup analyses indicated that significant moderating factors for developing empathy were age, country, scope of empathy measurement, type of empathy intervention, and presence of rehearsal. Moderating factors with limited evidence were sex, study quality, journal impact factor, and intervention characteristics. CONCLUSIONS: Despite heterogeneity and biases, empathy interventions in medical students are effective. These findings reinforce arguments in the literature and add considerable rigor from the meta-analysis. The authors propose a conceptual model for educators to follow when designing empathy interventions in medical students.