Given that over 97 percent of American teens play videogames, it is not surprising that many "games for health" target youth. Although tobacco use is the leading cause of preventable death in the United States, few digital games focus on preventing this behavior. The aims of this study were twofold: (1) to determine if youth will play a game with tobacco-related information and themes and (2) to explain the relationship between the truth(®) (Legacy, Washington, DC) campaign's "Flavor Monsters" gameplay and shifts in game-related tobacco knowledge, attitudes, and beliefs. First, two versions of the game, with different amounts of tobacco-related content, were developed to examine the influence of tobacco-related content on player engagement, length of play, awareness of the truth brand, and receptivity to the game. No statistically significant differences were found for engagement (P=0.81), length of play (P=0.10), or awareness of the truth brand (P=0.67). Using an online survey through a preexisting online panel of 13-24 year olds, a longitudinal (n=693) design was used whereby exposure to messages varied naturally over time. Because of the large number of anti-tobacco industry attitude questions, we created an Anti-Tobacco Industry (ATI) Index based on the results of a factor analysis. Although gameplay was not a predictor of lower levels of intention to smoke, level mastered was a significant positive predictor of ATI Index attitudes score at 3 months, controlling for baseline ATI Index score, age, gender, and ever cigarette use (P=0.002). Longitudinal findings indicate a cumulative and enduring effect, suggesting that anti-tobacco content can be successfully integrated within a mobile game to help increase anti-tobacco attitudes.