Substance use in immigrant youth frequently has been associated with different aspects of acculturation. There is inconsistency in the literature, however, about the direction of these relationships. Furthermore, seldom has the role of acculturation been examined in the context of other common substance use correlates, such as peer use and relationship with parents. Finally, the possible contribution of sense of school belonging previously has not been considered along with acculturation, peer use, and parent relationships, in explaining substance use and intentions to use in immigrant adolescents. Thus, the current study examined the extent to which levels of language and cultural acculturation, years in the country, sense of school belonging, relationship with parents, and friends’ use would account for their use and intentions to use substances in a sample of 166 Northeastern ninth grade urban Latino immigrant adolescents. Regression analysis revealed that language acculturation, sense of school belonging, and friends’ use were significantly associated with adolescent substance use and intentions to use. Consistent with past research in the general adolescent population, Latino immigrant youth who had fewer friends who use substances and had higher levels of school bonding/sense of school belonging were less likely to report using substances and/or having intentions to use. Contrary to previous literature examining non-clinical immigrant youth, the current study found that higher use of native language (low language acculturation) also predicted students’ use and intentions to use.