Background: Alternative (or continuation) high schools are institutions designed for students at risk for not graduating due to behavioral, educational, or medical problems. The present study explored the relationship between negative substance use consequences (eg, having trouble at school or work) and noncondom use in this at-risk population and whether these associations varied by sex. Methods: Participants (N = 1101; 62.9% Hispanic; M[subscript age] = 16.85) were sampled from 24 alternative high schools in California, and data were analyzed using cross-sectional multivariate logistic regression models. Results: We observed a relationship between the number of negative substance use consequences and probability of noncondom use at the last sexual encounter for boys (p < 0.001) but not girls (p > 0.05). There were significant associations between specific social consequences (missing school/work) and dependence symptoms (selling personal items to get alcohol or drugs) with noncondom use for boys only. There was a similar association between substance use frequency and noncondom use for boys. Conclusions: These findings suggest that substance use consequences may be a useful and advantageous indicator of risky sexual behaviors such as noncondom use for boys, but not girls, in alternative high school settings. Future research and intervention programming recommendations are discussed.