Substance abuse careers are episodic; with periods of abstinence and relapse are the prevailing patterns. This study was designed to identify patients who are relapse prone through certain relapse predictors that are often culturally colored. Two groups of Substance use disorder patients were compared; one group was abstinent for at least 6 months and the other was currently relapsed. They were all exposed to Addiction Severity Index (ASI), Structured clinical interview for Diagnostic and statistical manual of Mental disorder 4th edition for axis-I and II disorders (SCID- I and II), Social Readjustment Rating Scale (SRRS) and Religious Orientation Scale (ROS). The results suggested that the most significant predictors were the extent of drug use, the presence of comorbid psychiatric disorders or legal problems together with lower internal religiosity. Clinical implication of these results could assist therapists in constructing a preventive and therapeutic program for Substance use disorder. Moreover, consideration of these predictors could help in early identification of relapse prone patients with overall better outcome and improving patients’ quality of life.