The personality systems of Cloninger (as measured by the Tridimensional Personality Questionnaire [TPQ]) and Eysenck (as measured by the Eysenck Personality Questionnaire [EPQ]) both have been linked to substance use and abuse. The current study examined the predictive utility of both systems for substance use disorder (SUD) diagnoses, both cross-sectionally and prospectively. Participants (N = 489 at baseline) completed the EPQ and TPQ and were assessed via structured diagnostic interview at baseline and 6 years later (N = 457 at follow-up). Both the EPQ and TPQ scales demonstrated bivariate cross-sectional and prospective associations with SUDs. Within each system, those dimensions marking a broad impulsive sensation-seeking or behavioral disinhibition trait were the best predictors prospectively, although the 2 systems were differentially sensitive to specific diagnoses. These relations remained significant even with autoregressivity, other concurrent SUD diagnoses, and multiple personality dimensions statistically controlled.