OBJECTIVE: Little is known about how physical activity (PA), sedentary behavior, and various adolescent health risk behaviors are associated. The objective of this study was to examine relationships between PA and sedentary behavior patterns and an array of risk behaviors, including leading causes of adolescent morbidity/mortality. METHODS: Nationally representative self-reported data were collected (National Longitudinal Study of Adolescent Health; wave I: 1994-1995; II: 1996; N = 11957). Previously developed and validated cluster analyses identified 7 homogeneous groups of adolescents sharing PA and sedentary behaviors. Poisson regression predicted the relative risk of health risk behaviors, other weekly activities, and self-esteem across the 7 PA/sedentary behavior clusters controlling for demographics and socioeconomic status. Main outcome measures were adolescent risk behaviors (eg, truancy, cigarette smoking, sexual intercourse, delinquency), other weekly activities (eg, work, academic performance, sleep), self-esteem. RESULTS: Relative to high television (TV) and video viewers, adolescents in clusters characterized by skating and video gaming, high overall sports and sports participation with parents, using neighborhood recreation center, strict parental control of TV, reporting few activities overall, and being active in school were less likely to participate in a range of risky behaviors, ranging from an adjusted risk ratio (ARR) of 0.42 (outcome: illegal drug use, cluster: strict parental control of TV) to 0.88 (outcome: violence, cluster: sports with parents). Active teens were less likely to have low self-esteem (eg, adolescents engaging in sports with parents, ARR: 0.73) and more likely to have higher grades (eg, active in school, ARR: 1.20). CONCLUSIONS: Participation in a range of PA-related behaviors, particularly those characterized by high parental sports/exercise involvement, was associated with favorable adolescent risk profiles. Adolescents with high TV/video viewership were less likely to have positive risk behavior outcomes. Enhancing opportunities for PA and sport may have a beneficial effect on leading adolescent risk behaviors.