The past two decades have seen a transformation in youth programming toward a comprehensive positive youth development (YD) framework. Cool Girls, Inc., a YD program, focuses on improving girls' life chances by promoting positive behaviors and attitudes in multiple domains. These include self-concept, academic orientation, future orientation, and healthy behaviors. The present study uses a quasi-experimental, non-equivalent comparison group design to examine short-term effects of participation in Cool Girls, Inc. on multiple indicators of each of these domains. Participants were predominately African American and included 86 program participants and 89 comparisons in grades 4-8. Self-report questionnaires were administered at pretest (September-October) and posttest (April-May) of the 2005-2006 academic school year. We hypothesized that program participants would show improvements across domains of self-concept, academic orientation, future orientation, and healthy behavior. Relative to comparisons, program participants experienced gains in scholastic competence, hope for the future, and physical activity. Cool Girls participants with a mentor experienced significant gains in social acceptance and body image relative to other Cool Girls and were more than four times as likely to have expectations of avoiding drug use in the future. The role of mentoring as well as the study's practical significance, strengths, and limitations are discussed.