The aim of this study is to evaluate the efficacy of milnacipran in the acute treatment of patients with panic disorder. Thirty-one patients who met Diagnostic and statistical manual of mental disorders-IV criteria for panic disorder with or without agoraphobia were included in the study. Patients were initially treated with milnacipran 25 mg twice daily and then 50 mg twice daily until the 10th week. The treatment outcome and panic disorder severity were determined by the Panic Disorder Severity Scale, Panic Inventory, Clinical Global Impression and Hamilton Anxiety Scale, all of which were applied during every evaluation interview. Quality of life (WHOQOL-bref) was evaluated at baseline and at the end of the study. Missing data were handled by using the last observation carried forward for all participants who had taken at least one dose of study medication. Intention-to-treat was used in the analyses. Pharmacological treatment resulted in a clinically and statistically significant mean reduction in all severity measures. Remission (Clinical Global Impression < or = 2) was obtained in 58.1% of the sample. Regarding WHOQOL, we found a significant improvement (P<0.05) across treatment in all the domains studied. Although results may be influenced by the open design of this pilot study and by the small sample size, our findings suggest that milnacipran may be effective for the treatment of panic disorder and justify further research.