Objective: Given the prevalence of co-occurring risky sexual behavior and drinking among emergency department (ED) patients, we developed a motivational intervention (MI) to address both behaviors. This study tested efficacy of a single-session MI compared to brief advice (BA) for reducing heavy drinking and condomless sex in adult ED patients screening positive for both. Method: We randomized 372 patients to MI (n = 184) or BA (n = 188). Alcohol and sex risk outcomes were assessed over 9 months. Results: Generalized estimating equations models analyzing 327 patients with follow-up data provided strong support for efficacy of this integrated alcohol and sex-risk MI. Compared to BA, and after controlling for baseline covariates, those in MI reported significantly fewer heavy drinking days, drinks per week, and were less likely to engage in excessive drinking over follow-up (all ps < .05). MI was also favored over BA for reducing sex risk. Compared to BA, those in MI reported significantly fewer days on which they engaged in condomless sex with casual partners, had lower odds of reporting any condomless sex with a casual partner, and reported fewer days of sex under the influence of alcohol/other drugs (all ps < .05). Conclusion: This innovative MI was acceptable, feasible, and successfully delivered in 2 community hospitals and thus shows great promise for scalability and dissemination into complex health settings where newly insured at-risk individuals are likely to seek care.