Adolescent substance abuse can lead to detrimental long-term outcomes; thus, many schools have implemented programs to reduce both the incidence and prevalence of these issues. The "Botvin LifeSkills Training" (LST) program has demonstrated promising results in randomized controlled trials, but program results outside randomized trials have been mixed. This study examined the effectiveness of LST in modifying risk and protective factors and resultant alcohol, tobacco, and other drug use among 6th-grade students in schools in the mid-Atlantic region. Propensity score matching procedures were used to form equivalent exposure and non-exposure groups, and hierarchical linear models were used to examine main program effects and tests of moderation. Overall, hierarchical models demonstrated limited utility of LST when comparing results of 13 treatment schools (N[subscript students] = 1,052) to 10 control schools (N[subscript students] = 494). Significant moderation effects were observed such that boys gained stronger treatment effects than girls on risk factors related to friends' maladaptive behaviors, early drug use, lifetime cigarette use, and lifetime alcohol use. Unexpectedly, girls who received LST were more willing to use alcohol. Overall implications for practice and future study are also discussed. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://bibliotheek.ehb.be:2222/en-US/products/dissertations/individuals.shtml.]