AbstractWe examined multi‐system influences on risky sexual behavior measured by cumulative sexual risk index and number of nonromantic sexual partners among 4,465 single, sexually experienced adolescents. Hierarchical Poisson regression analyses were conducted with Wave I–II data from the National Longitudinal Study of Adolescent Health. Individual and family factors predicted both outcome measures. Neighborhood set predicted cumulative sexual risk index only, and peer factors predicted the number of nonromantic sexual partners only. School set did not predict either outcome. There were significant associations among risky sexual behavior, drug use, and delinquent behaviors. The results highlight the need for multifaceted prevention programs that address relevant factors related to family, peer and neighborhood influence as well as individual factors among sexually active adolescents. © 2010 Wiley Periodicals, Inc. Res Nurs Health 33:512–527, 2010