This study investigates gender differences in adolescent substance abuse behavior, treatment effectiveness, and the associated relationships with pre-, during-, and post-treatment groups of variables. Analyses were performed using 6-month post-treatment follow-up data from over two thousand subjects. T-test analysis showed that females exhibited more psychological difficulties, family-related problems, and sexual abuse experiences, whereas males exhibited worse school and legal problems before treatment. Females also showed better attendance in aftercare or self-help groups and better treatment outcomes than males. Discriminant function analyses indicated that school problems, legal problems, lack of religious involvement, and substance abuse before treatment could discriminate abstinence status for females at 6-month follow-up. Substance abuse before treatment, length of stay, and parental participation in treatment could differentiate abstinence status for males at 6-month follow-up. Limitations in applying research findings and implications for adolescent substance abuse treatment are also discussed.