In a recent randomized field trial, Ellickson et al. found the Project ALERT drug prevention curriculum curbed alcohol misuse and tobacco and marijuana use among eighth-grade adolescents. This article reports effects among ninth-grade at-risk adolescents. Comparisons between at-risk girls in ALERT Plus schools (basic curriculum extended to ninth grade with five booster lessons) and at-risk girls in control schools showed the program curbed weekly alcohol and marijuana use, at-risk drinking, alcohol use resulting in negative consequences, and attitudinal and perceptual factors conducive to drug use. Program-induced changes in perceived social influences, one's ability to resist those influences, and beliefs about the consequences of drug use mediated the ALERT Plus effects on drug use. No significant effects emerged for at-risk boys or at-risk adolescents in schools where the basic ALERT curriculum (covering seventh and eighth grades only) was delivered. Possible reasons for gender differences and implications for prevention programming are discussed.