Objective: The purpose of this research is to evaluate the efficacy and tolerability of Moclobemide and Alprazolam in treatment of panic disorder. Method: A randomized double-blind controlled trial was conducted and one instrument for collection data was developed. One hundred and eighty six panic disorder patients were enrolled for 8 week treatment period. Ninety three patients were given Alprazolam and Ninety three patients were given Moclobemide. The total panic attacks occurred in each week after intervention was recorded by patient in Panic Self-report Inventory (Diary record from). All of panic attacks were identified and counted by a psychiatrist according to DSM-IV criteria. The efficacy of Moclobemide and Alprazolam in reducing the panic attacks were analyzed by using poisson regression and Generalized Estimating Equations (GEE). Result: The incidence of panic attacks was decreased by the first week of both treatment groups and this decreasewas maintained until the end of study. At week 1 Alprazolam showed efficacy in reducing panic attacks more than Moclobemide, the difference of incidence rate = 0.96 (95%CI = 0.36-1.55) but After week 3 Moclobemide became more effective than Alprazolam, the difference of incidence rate at week 4 to week 8 = -0.42[95%CI = (-0.62)-(-0.24)], -0.27[95%CI = (-0.42)-(-0.13)], -0.44[95%CI = (-0.61)-(-1.55)], -0.7[95%CI = (-0.29)-(-0.05)], and -0.22[95%CI = (-0.34)-(-0.11)] respectively. Analysis by using GEE when adjusted baseline, age, and sex the adjusted incidence rate ratio was 0.88 (95%CI = 0.76-1.02) P-value = 0.084. Conclusion: Greater improvement in panic attacks in patients given Moclobemide and Alprazolam was shown by the end of the first week of treatment and sustained throughout the 8th week. There is no significant difference in the efficacy of Moclobemide and Alprazolam in reducing panic attacks.