Background: Most psychiatric programs provide lectures on basic principles of psychopharmacology. Yet, this traditional approach has been criticized due to excessive information and passive transfer of expert knowledge. An alternative teaching method is the use of "academic games." Aims: To investigate medical students' acquisition of knowledge on psychopharmacology, and their perception of a game playing approach compared to traditional lectures. Methods: Two senior residents designed, implemented, and executed a randomized pretest-posttest study to teach psychopharmacology, using an academic game and a lecture format, to third-year medical students during a 6-week Psychiatry clerkship. Both didactic interventions were delivered concurrently for five consecutive weeks covering five psychopharmacology modules: antidepressants I (selective serotonin reuptake inhibitors and atypical antidepressants), antidepressants II (monoamine oxidase inhibitors and tricyclic antidepressants), mood stabilizers, antipsychotics, and anti-anxiety agents/sedatives/hypnotics. The game follows similar rules of the famous TV show, "Jeopardy" using a power point grid and a multiple choice question format. Results: Forty-three medical students participated (29 assigned to the game approach, 14 to the traditional lecture approach). None of the demographic variables (age, gender, years after graduation, Graduate Point Averages, and United States Medical Licensing Examination 1) were significantly associated with the pre/posttest score difference between groups. Both groups improved their knowledge on psychotropic drugs [(game group t = 10.86, p < 0.001); control t = 4.82, p < 0.001)] throughout the 6-week Psychiatry rotation. Students in the game group had a better perception of this educational method as measured by perceived enjoyment, increased knowledge of psychopharmacology, and stimulating interest in the subject compared to those in the lecture group (p < 0.05). Conclusions: Teaching psychopharmacology in medical students by using academic games can make the learning experience more enjoyable and motivating; however, future studies with higher quality methodology and design are needed to determine the role of educational games in acquiring new psychopharmacological knowledge. © 2011 Informa UK Ltd All rights reserved.