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Female substance abusers recruited from the community were randomly assigned to receive 1 of 3 brief interventions that differentially targeted their personality and reasons for drug use. The 90-min interventions were: (a) a motivation-matched intervention involving personality-specific motivational and coping skills training, (b) a motivational control intervention involving a motivational film and a supportive discussion with a therapist, and (c) a motivation-mismatched intervention targeting a theoretically different personality profile. Assessment 6 months later (N = 198) indicated that only the matched intervention proved to be more effective than the motivational control intervention in reducing frequency and severity of problematic alcohol and drug use and preventing use of multiple medical services. These findings indicate promise for a client–treatment matching strategy that focuses on personality-specific motives for substance abuse.