Objectives: To quantify the depiction of violence, blood, sexual themes, profanity, substances, and gambling in video games rated M (for "mature") and to measure agreement between the content observed and the rating information provided to consumers on the game box by the Entertainment Software Rating Board. Design: We created a database of M-rated video game titles, selected a random sample, recorded at least 1 hour of game play, quantitatively assessed the content, performed statistical analyses to describe the content, and compared our observations with the Entertainment Software Rating Board content descriptors and results of our prior studies. Setting: Harvard University, Boston, Mass. Participants: Authors and 1 hired game player. Main Exposure: M-rated video games. Main Outcome Measures: Percentages of game play depicting violence, blood, sexual themes, gambling, alcohol, tobacco, or other drugs; use of profanity in dialogue, song lyrics, or gestures. Results: Although the Entertainment Software Rating Board content descriptors for violence and blood provide a good indication of such content in the game, we identified 45 observations of content that could warrant a content descriptor in 29 games (81%) that lacked these content descriptors. M-rated video games are significantly more likely to contain blood, profanity, and substances; depict more severe injuries to human and non-human characters; and have a higher rate of human deaths than video games rated T (for "teen"). Conclusion: Parents and physicians should recognize that popular M-rated video games contain a wide range of unlabeled content and may expose children and adolescents to messages that may negatively influence their perceptions, attitudes, and behaviors.