A prospective study of the role of comorbid substance abuse and dependence and mood disorders in the outcome from pathological gambling. A naturalistic sample of pathological gamblers who had recently quit gambling (N = 101) was followed and data were available for 83% of participants at 3 months, 80% at 12 months, and 52% at 5 years. Those participants with a drug diagnosis during their lifetime were less likely to have a minimum 3 month period of abstinence, and those who had been involved in gambling treatment were more likely to have a minimum 12 months of continuous abstinence. Lifetime gambling problem severity and involvement in gambling treatment were most commonly associated with a shorter time to achieving a period of abstinence of any length. Lifetime history of a mood disorder also predicted a longer time to reach a minimum 3 months of continuous abstinence. Both gambling treatment and an alcohol diagnosis follow up predicted an increase in the odds of experiencing a relapse from a minimum 6 month period of abstinence. Overall, comorbid mental health disorders are predictive of shorter term but not longer term outcome.