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Objective: Withdrawal symptoms are a main reason of continuous use of opioid. This study compares the efficacy of augmentation of amantadine with clonidine in decreasing opioid withdrawal symptoms. Methods: This double-blind randomized clinical trial was carried out in the detoxification and rehabilitation inpatient ward at Razi Hospital, Tabriz, Iran during 2012. The patients were randomly assigned to receive clonidine or clonidine plus amantadine; and withdrawal symptoms were evaluated in the admission day and 24, 48, and 72 hours later. Data were analyzed using SPSS by the 2*2 repeated analyses of variances (ANOVA). Results: From the total of 69 participants, 30 patients completed the trial in each group. The severity of symptoms, however, had an increasing trend in both groups. Analysis of variance of the symptom severity score (by The Clinical Opiate Withdrawal Scale) revealed a significant group-time interaction, and the patients who were receiving amantadine experienced milder symptoms . Conclusions: Treatment of opioid withdrawal symptoms with amantadine and clonidine would result in a better outcome compared with clonidine alone.