Background: Physician empathy has been associated with improved clinical outcomes and lower physician burnout. We evaluated whether forum theater (FT), a form of applied drama that allows participants to enter the performance and represent the actions associated with emotions, would foster empathy in medical students, and which underlying variables would be associated to empathy scores. Methods: Three classes totaling 488 fourth-year medical students participated in the study. Forum theater was used to explore difficult encounters with patients and family members: announcement of cancer, fall at home of an elderly person requiring hospitalization, appointment with a patient suffering from depression, announcement of diabetes in an adolescent. The first scene was played by actors in front of a group of students, then audience members were asked to enter the performance and, by taking over the role of the "physician-actor," to explore alternative interactions. All the students followed two sessions as actors and observers in random order and were randomly assigned to FT sessions after 36 or 56 weeks of clinical rotations. They completed the Jefferson Scale of Physician Empathy (JFSE) anonymously. Results: Students were 22.1 ± 1.5 years old (43% males). Empathy scores increased after each session: 102.0 ± 9.8 before the sessions, 106.3 ± 9.8 after session 1 and 107.8 ± 11.5 after session 2 (p < 0.05). In regression models, gender (F vs. M, + 3.0 ± 1.0, p < 0.001) and position in the session (actor vs. observer, + 2.1 ± 1.0, p < 0.05) were significant determinants of JFSE scores, whereas age, session theme, and duration of clinical rotation were not. Conclusion: Being an actor in forum theater was a valuable tool for enhancing empathy scores in medical students.