This study examined client background characteristics, substance use severity, and psychological distress in relation to return to alcohol and drug use among men and women 2 years following substance user treatment. Participants (n = 180) completed a baseline interview within their first month of substance user treatment (conducted in 1995/1996) and follow-up interview 2 years following the baseline interview (conducted in 1997/1998). Structural equation modeling analyses were used to examine the relationship among client background characteristics and problem severity indicators, measured during treatment, in relation to alcohol and illicit drug use 2 years posttreatment. Psychological distress directly predicted alcohol and illicit drug use during follow-up and appeared to mediate the relationship between client background characteristics (such as gender, race, and marital status) and substance use consequences on posttreatment substance use. Income directly predicted alcohol use and age directly predicted illicit drug use, regardless of problem severity (including psychological distress and substance use consequences). Results support long-term clinical monitoring of psychological distress as a marker for return to drug or alcohol use.