The purpose of this study is to utilize the Extended Parallel Process Model (EPPM) to expand the construct of efficacy in the adolescent substance use context. Using survey data collected from 2,129 seventh-grade students in 39 rural schools, we examined the construct of drug refusal efficacy and demonstrated relationships among response efficacy (RE), self-efficacy (SE), and adolescent drug use. Consistent with the hypotheses, confirmatory factor analyses of a 12-item scale yielded a three-factor solution: refusal RE, alcohol-resistance self-efficacy (ASE), and marijuana-resistance self-efficacy (MSE). Refusal RE and ASE/MSE were negatively related to alcohol use and marijuana use, whereas MSE was positively associated with alcohol use. These data demonstrate that efficacy is a broader construct than typically considered in drug prevention. Prevention programs should reinforce both refusal RE and substance-specific resistance SE.