On the basis of a large-scale survey of high-school youth, the authors compared adolescents reporting exclusively heterosexual, mostly heterosexual, bisexual, and predominately same-sex attraction based on high-risk involvement across a range of risk behaviors. Bisexual and same-sex attracted groups were characterized by heightened high-risk involvement relative to the other two groups. Mediation analysis was used to determine whether these group disparities were explained by a set of normative predictive factors spanning multiple life domains. Differences among a combined exclusively/mostly heterosexual attraction group and both the bisexual and same-sex attraction groups were attenuated (66% and 50%, respectively) after incorporating the hypothesized intervening predictive factors, providing evidence of partial mediation. Primary mediators included intrapersonal (attitudes toward risk-taking; academic orientation), interpersonal (peer victimization; parental relationships; unstructured activities), and environmental (substance availability) factors. Mediation results were consistent across participant age and sex. Implications, limitations, and directions for future research are discussed.