Changes in psychosocial risk and protective factors associated with the onset of substance use were examined in a sample of 556 urban public school sixth graders. General linear modeling analyses indicated that students who did not use substances by the end of sixth grade consistently had higher scores on protective factors than did students who were already using substances at the beginning of sixth grade. Students who began to use during the school year were in flux with scores similar to nonusers at Time 1 and scores closer to early users by Time 2. These findings suggest that interventions which focus on skill enhancement during the transition to middle school may be effective at delaying the onset of substance use. Editors' Strategic Implications: The authors find the same protective factors in this urban, primarily African American sample that are typical in suburban, White samples. Developmentalists and school officials will find interesting the changing effects of protective factors against early substance use during the transitional sixth grade year.