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Oxcarbazepine as an anticonvulsant has been suggested as an effective drug in affective disorders. The present study was designed to compare the efficacy of oxcarbazepine and sodium valproate in the treatment of acute mania in the Iranian population. In a double-blind, randomized clinical trial, hospitalized bipolar patients in the acute manic phase who were admitted to Ibn-e-Sina psychiatric hospital in Mashhad city (north-eastern part of Iran) were enrolled. The diagnosis was confirmed using Structured Clinical Interview for DSM-IV-TR. Patients were then randomly allocated into two groups taking oxcarbazepine (900-2400 mg/day) and sodium valproate (about 20 mg/kg/day) for 6 weeks. Young Mania Rating Scale (YMRS), Clinical Global Impression Scale (CGI-S), and adverse effects of drugs were assessed at baseline and after 3 and 6 weeks. Mania symptoms based on mean scores of YMRS and CGI-S significantly decreased from baseline to endpoint in both treatments (P0.01). However, there was no significant difference between the two groups in terms of reduction of symptoms during times (P = 0.715 and P = 0.446, respectively) and adverse events (P0.05). This study confirmed the previous findings that indicate the efficacy of oxcarbazepine as same as sodium valproate. Moreover, its adverse effects resemble sodium valproate in the treatment of acutely manic patients.