BACKGROUND: Although adolescence is a time when physical activity levels decline, few interventions have targeted high school-aged girls in the school setting. OBJECTIVE: To evaluate the effects of a life skills-oriented physical activity intervention for increasing overall physical activity in high school-aged girls. DESIGN: Randomized controlled trial. SETTING: Baltimore magnet high school. PARTICIPANTS: A total of 221 ninth-grade girls, 83.0% of whom were African American. Intervention Participants were randomized to an 8-month physical intervention conducted in physical education class or to a standard physical education class (control). MAIN OUTCOME MEASURES: Self-reported estimated daily energy expenditure (physical activity), self-reported sedentary activities (television viewing and computer or Internet use), cardiorespiratory fitness, and selected cardiovascular disease risk factors. RESULTS: Intervention classes spent 46.9% of physical education class time in moderate to vigorous activity compared with 30.5% of time for control classes (P<.001). There were no significant between-treatment group differences for mean daily energy expenditure (P = .93), moderate-intensity energy expenditure (P = .77), or hard to very hard energy expenditure (P = .69). The proportion of participants who spent 3 or more hours viewing television during school days declined from 22.3% to 17.0% in the intervention group, but remained at 26.7% for the control group (P = .03). Both groups improved their cardiorespiratory fitness (P<.001). CONCLUSION: A life skills-oriented physical education curriculum may need to be combined with other approaches to increase the magnitude of effects on physical activity behavior in predominantly African American high school-aged girls.