This study examined the clinical utility of the Cross-Cultural (Chinese) Personality Inventory (CPAI-2) in differentiating the personality characteristics of Chinese men with substance use disorders from other psychiatric patients and normal control participants. The CPAI-2 profile of 121 Chinese men with substance use disorders was contrasted with that of a matched psychiatric comparison group (n = 172) and a normal comparison group (n = 187). Multivariate analyses of variance and logistic regression results supported the utility of the CPAI-2 clinical scales, especially Pathological Dependence, Antisocial Behavior, and Depression, for assessing substance use disorders. The Pathological Dependence scale (cutoff T score of 64) achieved good sensitivity and specificity. Apart from the universal personality traits related to neuroticism, conscientiousness, and agreeableness found in Western studies, the indigenously derived CPAI-2 personality scales, including Family Orientation and Harmony, highlighted deficits in social adjustment and interpersonal relationship as important cultural features in the personality characteristics of these participants. The study provided a cross-cultural extension to research on the relationship between personality and substance use disorders and could assist clinicians in considering culturally relevant treatment approaches.