Background: A number of drugs are used to control opioid withdrawal symptoms during detoxification. Tramadol, as a partial opioid agonist, has been widely used to manage acute and chronic pains. The present study was designed to assess the effectiveness of tramadol in methadone-assisted detoxification. Methods: In a double-blind randomized clinical trial 72 opioid-dependent patients as defined by 4th edition of the Diagnostic and Statistical Manual of Mental Disorders were assigned to two groups receiving methadone (15 mg/day) or tramadol (560 mg/day). Patients in both groups received clonidine and oxazepam. The severity of withdrawal symptoms was assessed at the baseline and 7 times every other day onward using the Short Opioid Withdrawal Scale (SOWS). Results: Mean scores of total withdrawal symptoms on days 13th and 15th were significantly higher in the methadone group than in the tramadol group (16.2±9.5 vs 9.5±7.5 and 15.2±10.6 vs 8.5±6.9). On day 15th, the patients in methadone group showed significantly more severe psychological symptoms (5.8± 4.1 vs 4.3± 4.2). In the methadone group mean score of psychological symptoms was higher on day 15th compared with the first day (15.2±10.6 vs 9.7±8.7). Drowsiness and sweating were significantly more in patients in methadone group than in tramadol group. Conclusion: Tramadol can be used effectively as a substitute drug in opioid-assisted detoxification, particularly in patients with low to moderate dose opioid dependency.