The deleterious effects of early substance use have been well documented. Past research has produced mixed results regarding the extent to which the profile of risk differs for urban African American and suburban Caucasian youth. Sixth graders from urban (n = 420; 92% African American) and suburban (n = 391; 89% Caucasian) schools in metropolitan Detroit completed surveys at the beginning and end of the school year. More similarities than differences were found in hierarchical multiple regression analyses predicting substance use among these two groups of students. For both groups, peer pressure susceptibility and school commitment were significantly related to substance use. For girls only, participation in after-school activities was negatively associated with substance use. The importance of prevention programs in the transition to middle school is discussed.