Introduction: Rates of drug use among early adolescent girls meet or exceed rates of their male counterparts. Girls are also vulnerable to differential risk factors for drug use. Yet, expressly designed prevention programs targeting this population are absent. The present study reports 2and 3-year findings on a web-based drug abuse prevention program for adolescent girls. Methods: A sample of adolescent girls (N = 788) were recruited via Facebook. Online, all girls completed pretests; girls were randomly assigned to a 9-session intervention arm or to a measurement-only control arm and all girls completed posttests. All girls also completed 1-, 2-, and 3-year follow-up measurements. Results: At 2-year follow-up and compared to girls in the control arm, intervention-arm girls reported less past-month cigarette, marijuana, and "other' drug use (club drugs, cocaine, ecstasy, hallucinogens, heroin, inhalants, methamphetamines, steroids, prescription drugs), lower rates of peer drug use, and increased scores on drug refusal skills, coping skills, self-esteem, media literacy, and self-efficacy. At 3-year follow-up, and compared to girls in the control arm, intervention-arm girls reported less past-month cigarette and e-cigarette use, lower rates of peer drug use, lower reported anxiety and stress, and increased scores on drug refusal skills, selfesteem, media literacy, self-efficacy, and body image. Conclusions: Longitudinal outcome data lend support to the efficacy of a gender-specific, webbased drug abuse prevention program to reduce adolescent girls' drug use rates and associated risk factors.