Background: Over-the-counter (OTC) drug use is an increasing health issue among adolescents. Purpose: This study investigated OTC drug use among 7th through 12th grade multiracial students in one metropolitan area. Methods: A total of 2134 students completed the PRIDE Questionnaire, which examines alcohol and other drug use. Results: A total of 8.3% of multiracial students reported using OTC drugs in their lifetime. Students involved in prosocial activities and those reporting positive parent factors were significantly less likely than their counterparts to use OTC drugs. Teacher and school factors were associated with reduced odds of use for males and high school students. Conversely, engaging in risky behaviors and having friends who used alcohol, tobacco, or marijuana significantly increased the odds for OTC drug use among males, females, junior high, and high school students. Discussion: Several risk and protective factors for OTC use were identified and, as such, should be addressed in prevention programming. Translation to Health Education Practice: Health education professionals should implement OTC drug use initiatives for multiracial youth that aim to reduce risk factors and increase protective factors against use. In addition, parents should be incorporated into prevention efforts because parent factors were important in reducing drug use among youth.