Researchers have developed many different computerized interventions designed to teach students about the dangers of substance use. Following in this tradition, we produced a series of video games called Bacon Brains. However, unlike many other programs, ours focused on the “Science of Addiction,” providing lessons on how alcohol and other drugs affect the brain. The purpose of this study was to evaluate the effectiveness of our games in teaching students our science-based curriculum. We enrolled over 200 students and randomly assigned them to play our games or a different series of NIDA-produced games. Of the students in the Bacon Brains conditions, half were instructed to play collaboratively and the other half was told to play competitively. Results indicate significantly greater knowledge gains among students in Bacon Brains compared to the existing games (5.01 mean knowledge score difference; [F(1,242)=9.588, p=.002]). Girls demonstrated knowledge gains in both collaborative and competitive conditions, but boys demonstrated similar gains only in the competitive condition. Based on our outcomes, we conclude that video games can serve as an effective method of science instruction. We further discuss the importance of considering gender differences in light of differential response to collaborative vs. competitive learning environments.