Objective To evaluate gender differences in the clinical presentation of generalized anxiety disorder (GAD) and response to sertraline treatment. Methods Adult outpatients who met DSM-IV criteria for GAD with a minimum Hamilton rating scale for anxiety (HAM-A) total score ! 18 were randomized to 12 weeks of double-blind treatment with flexible doses (50-150 mg) of sertraline (n ΒΌ 182; female, 59%) or placebo (n ΒΌ 188; female, 51%). Results Clinical presentation of GAD was very similar in men and women in terms of the severity of the HAM-A psychic factor, severity of concomitant depression symptoms, duration of GAD, quality of life and impairment in physical health. Women had an earlier age of onset and higher HAM-A somatic factor scores compared with men. For both men and women, treatment with sertraline resulted in greater change from baseline to endpoint on the HAM-A compared with placebo (adjusted change AE SE: men: Γ12.1 AE 0.9 vs Γ8.8 AE 0.9; women: Γ11.4 AE 0.8 vs Γ7.1 AE 0.9, p < 0.001); the interaction between gender and treatment group was not significant, nor was there a significant difference between the average change from baseline for men compared with women. Similarly, responder rates based upon clinical global impression-improvement (CGI-I) scores at endpoint showed no significant interaction between gender and treatment, nor was there a significant difference in the response rates by gender; however, the response rate of sertraline compared with placebo was significantly different (p < 0.0001) (men: 64% vs 40%; women: 62% vs 34%). Similar findings were evident at week 4 assessment and for completers (week 12). Overall, sertraline was well tolerated by both men and women. Conclusion Women and men with GAD showed similar clinical presentations, with the exception that women had an earlier age of onset and reported more somatic anxiety symptoms. Sertraline was an effective and well tolerated treatment for GAD in both men and women.