We examined the association between psychopathy, assessed using the Hare Psychopathy Checklist-Revised (PCL-R—Hare, 1991), and substance use in a sample of 200 male federal prison inmates. Psychopathy diagnoses were not significantly comorbid with alcohol or drug use disorders. However, dimensional PCL-R scores were correlated with DSM-III-R diagnoses of drug abuse/dependence, the number of different drugs tried, age at first alcohol intoxication, and the number of drug-related charges and convictions. A meta-analysis of four studies looking at dimensional PCL-R scores and substance use revealed that the association was highly consistent across studies and moderate in magnitude for drug use disorders but somewhat inconsistent and weaker in magnitude for alcohol use disorders. Analyses using the PCL-R factors yielded results consistent with the suggestion that substance use is associated with an unstable, antisocial life-style rather than with the interpersonal and affective characteristics of psychopathy.