The aim of the present study was to determine which domains in NEO Personality Inventory-Revised would predict relapse and dropout in treatment-seeking slot-machine pathological gamblers after 1-year follow-up. The NEO PI-R was completed by 73 consecutive treatment-seeking outpatients before they began an open program of individual cognitive-behavioral therapy. Twelve months after starting treatment, patients were categorized in groups as abstinent versus relapsed or completers versus dropouts. At 1-year follow-up, 29% of patients were abstinent, and 48% had completed treatment. Those who had relapsed showed higher significant scores on Neuroticism and lower scores on Conscientiousness. The dropout group scored significantly higher on Neuroticism and lower on Agreeableness and Conscientiousness than the completer group. Low scores on Conscientiousness emerged as a significant predictor of relapse; while low scores on Conscientiousness and Agreeableness were significant predictors of dropout. It seems as if low Conscientiousness could be considered as a predictor of treatment failure measured by either relapses or dropouts, whereas, low Agreeableness seems to be a prognostic domain specifically for dropouts. Pathological gamblers with lower Conscientiousness and lower Agreeableness seem to be at risk of prematurely dropping out of treatment. Our findings support the importance of individual differences in personality on therapy outcomes. The NEO PI-R may constitute an important tool to identify treatment-seeking pathological gamblers who may be at risk of relapsing or dropping out of treatment.