This trial was to evaluate the efficacy and tolerability of venlafaxine extended release (XR) and paroxetine for treatment of patients with generalized anxiety disorder (GAD). Sixty patients who met DSM-IV criteria for GAD were randomly assigned to either venlafaxine XR or paroxetine for 8 weeks. Efficacy was assessed with the Hamilton Rating Scale for Anxiety (HAM-A) and Clinical Global Impression-Severity of Illness (CGI-S) scale at the baseline, week 1, week 4, and week 8. The side-effects were collected with reported adverse events and laboratory tests throughout the study period. Repeated measures analysis of variance (ANOVA) on the HAM-A and CGI-S scores showed a significant decrease over time in both treatment groups without significant group difference or time x group interaction effect. There were no serious adverse events in both groups. This open trial demonstrated that either venlafaxine XR or paroxetine would be effective and tolerable for the treatment of patients with GAD. Double blind, placebo-controlled head-to-head comparison studies are needed to draw a definite conclusion.