Study Objectives: To assess the impact of a resident-driven sexual health educational initiative in an inner-city Cleveland middle school. Design, Setting, and Participants: 10 resident physicians and 57 students in 7th and 8th grade participated in this prospective cohort study. Interventions and Main Outcome Measures: Residents taught 3 sessions on the topics of basic anatomy and physiology, pregnancy, sexually transmitted infections (STI), contraception, and safe relationships. Outcome measures included the percentages of students able to name at least 3 different STIs and contraceptive methods; to name potential complications of STIs; and to correctly identify condoms and abstinence as the only contraceptive methods also protective against STI transmission. Results: Significant improvements were noted in students' baseline knowledge of human anatomy, contraception, and safe sex practices after completion of the curriculum. The percentage of students able to name at least 3 forms of birth control increased from 1.7% to 70.7% (P < .0001). The percentage able to name at least 3 different STIs increased from 5.3% to 72.4% (P < .0001). Follow-up testing 4 months after completion of the curriculum demonstrated significant knowledge retention. All residents and medical students surveyed described a perceived need for comprehensive rather than abstinence-based reproductive health education in schools. Conclusions: The socioeconomic burden of teen pregnancy justifies comprehensive efforts to improve reproductive health education.