Objective: Young people in urban areas are often the focus of pregnancy and sexually transmitted infection (STI) prevention programmes because of their high risk of unwanted pregnancy and contracting an STI. Young people in rural areas are far less studied but also have a high risk of similar outcomes. This study evaluates Giving Our Girls Inspiration & Resources for Lasting Self-Esteem (GO GIRLS), an after-school pregnancy and STI prevention programme, in a sample of high-risk middle school girls living in rural areas using quasi-experimental methods. Design: GO GIRLS was assessed using the same survey administered at three time points--prior to the start of the programme, directly following completion of the programme and at the end of the school year. The sample for this study was drawn from a larger evaluation of a multi-faceted health initiative conducted over the course of the school year in three rural counties in South Central Florida. Setting: The GO GIRLS programme was implemented in a rural area of South Central Florida. This area has higher rates of teenage pregnancy and poverty and lower educational attainment in comparison with state averages. Method: Propensity scores and nearest-neighbour matching without replacement were used to select a group of girls who did not participate in the programme but were comparable to participants. Programme participants were compared to the propensity score-selected controls on key outcomes using hierarchical linear regression. Results: Findings indicate that at follow-up, girls who participated in GO GIRLS had attitudes more accepting of delaying sexual intercourse than controls. However, participants did not differ in their levels of sex refusal skills at follow-up. Conclusion: This study shows that the GO GIRLS programme has promise for at-risk, rural girls and highlights where future evaluation research is needed.