Relapse is a typical feature of heroin addiction and rooted in genetic and psychological determinants. The aim of this study was to evaluate the effect of personality traits, impulsivity, and COMT gene polymorphism (rs4680) on relapse to heroin use during 5-year follow up. 564 heroin dependent patients were enrolled in compulsory drug rehabilitation center. 12 months prior to their release, personality traits were measured by BIS-11 (Barratt Impulsiveness Scale-11) and Temperament and Character Inventory (TCI). The COMT gene rs4680 polymorphism was genotyped using a DNA sequence detection system. The heroin use status was evaluated for 5 years after discharged. Among the 564 heroin-dependent patients, 500 were followed for 5 years after discharge and 53.0% (n¼265) were considered as relapsed to heroin use according to a strict monitor system. Univariate analysis showed that age, having ever been in methadone maintenance treatment (MMT), the total scores and nonplanning scores of BIS-11, and the COMT rs4680 gene variants were different between relapse and abstinent groups. Logistic regression analysis showed higher BIS total score, having ever been inMMTand younger first heroin use age are the predictors of relapse to heroin use during 5 years follow-up, and theCOMT rs4680 gene had an interaction with BIS scores. Our findings indicated that the impulsive personality traits, methadone use history, and onset age could predict relapse in heroin-dependent patients during 5 year’s follow up. The COMT gene showed a moderational effect in part the relationship of impulsivity with heroin relapse.