The prevention of underage drinking and related outcomes focuses on strengthening protective factors. Using data from the National Longitudinal Study of Adolescent Health ( N = 3,862), the authors examine the effects of protective factors from three domains of adolescents' lives (individual, familial, and extrafamilial) on experiencing negative consequences of alcohol use, while controlling for relevant risk factors, among youth who have already started drinking. Results showed that protective factors had relatively little influence on not experiencing negative alcohol-related consequences, regardless of social context. One individual protective factor, strategic decision making, was related to negative drinking outcomes in cross-sectional models. In longitudinal models, maternal attachment reduced the likelihood of experiencing negative outcomes over time. The effects of the risk factors remained strong in all models. Findings suggest "mixed-methods" preventive approaches, attending to risk factors, and including strategies to strengthen protective factors across multiple domains of adolescents' lives when striving to affect negative drinking-related outcomes. (Contains 4 tables.)