['Examine the validity of preference-weighted health-related quality of life measures in a sample of substance use disorder (SUD) patients. The implications of cost-utility analyses (CUAs) of SUD interventions are discussed.', 'Cross-sectional analysis of subjects seeking SUD treatment.', 'Seven SUD treatment centers in a medium-sized Midwestern metropolitan area in the United States.', 'Data from 574 SUD subjects were analyzed from a study to test interventions to improve linkage and engagement with substance abuse treatment.', 'Subjects completed the following preference-weighted measures: self-administered Quality of Well-Being scale (QWB-SA) and Medical Outcomes Study SF-12 (standard gamble weighted or SF-12 SG); and clinical measures: Addiction Severity Index (ASI) and a symptom checklist based on the DSM-IV.', 'In unadjusted analyses, the QWB-SA was correlated significantly with six of seven ASI subscales and the SF-12 SG was correlated with four of seven. In adjusted analyses, both preference-weighted measures were significantly correlated with diagnostic, physical health, mental health and drug use measures, but not with legal or alcohol use measures. The QWB-SA was also correlated with employment problems and the SF-12 SG was correlated with family/social problems.'] Do preference-weighted health-related quality of life measures and substance use disorder severity?