OBJECTIVES: This study assessed the effect of treatment with venlafaxine extended release (XR), paroxetine and placebo on health related work productivity among panic disorder patients. METHODS: In a multicenter, double-blind trial, patients with DSM-IV panic disorder were randomly assigned to fixed-dose (75mg/day or 225mg/day) venlafaxine XR, paroxetine (40mg/day), or placebo for a maximum of 12-weeks. Secondary analyses focused on health-related work productivity impairments as measured by the Work Limitations Questionnaire (WLQ). WLQ has 25 items in four limitation dimensions (time, physical, mental-interpersonal, and output demands). Treatment-related improvements at final-on-therapy (FOT) and week 12 were compared using analysis of covariance adjusting for baseline impairment score and center. RESULTS: Venlafaxine XR 225mg was associated with significantly greater improvement from baseline, relative to placebo, on all subscales of WLQ (P<0.005) except physical demands. At the FOT assessment, venlafaxine XR 75mg showed significant improvement compared with placebo in time management (P<0.05), marginally significant improvement in mental/interpersonal demands (P=0.059) and output demands (P=0.054), and no significance for physical demands. Paroxetine failed to show significant improvement relative to placebo on all WLQ subscales in the FOT assessment. CONCLUSION: Venlafaxine reduced work impairment compared to placebo. Paroxetine did not separate from placebo.