Background:Substance abuse or drug addiction is one of the most important health issues in every society, which can lead to physical and mental problems.Objectives:This study aimed to compare the efficacy of tramadol plus gabapentin versus methadone use in the treatment of opiate withdrawal.Patients and Methods:Consenting male subjects who fulfilled the DSM-4 criteria for opiate dependence syndrome (opium, residue, and heroin) were randomly assigned in two groups to receive tramadol plus gabapentin or methadone. Assessment tools were Adjective Rating Scale for Withdrawal (ARSW), Clinical Opiate Withdrawal Scale (COWS) and Visual Analogue craving Scale (VAS). Fifty-nine subjects were enrolled and evaluated on days 1, 2, 3, 4, 6, and 8 during their 10 days of admission. Twenty-nine participants received methadone and the other 30 received tramadol plus gabapentin for their treatment.Results:Mean (SD) age of the patients in methadone group and tramadol plus gabapentin group were 33.9 (7.1) and 32.4. (8.1), respectively (P = 0.462). The overall ARSW (P value = 0.263) and COWS (P = 0.862) scores between the two groups were comparable. The differences in the VAS score for craving between the two groups was marginally significant (P = 0.057). The highest VAS score was at the third day of admission in both groups and it was generally higher in methadone group.Conclusions:The severity of withdrawal syndrome in two groups was not significantly different. The craving was higher in the group receiving methadone from the second day of admission even though the usage amount was higher in the tramadol plus gabapentin group. The findings of this study suggest that the combination of tramadol plus gabapentin is an efficient method for opioid detoxification.