Objective: To examine whether duloxetine was effective in improving anxiety symptoms, pain severity, and functioning in adults with DSM-IV-defined GAD presenting with clinically significant painful physical symptoms. Method: Results were pooled from two randomized, double-blind studies evaluating duloxetine 60 to 120mg once daily versus placebo. The primary efficacy measure was mean change from baseline-to-endpoint using the Hamilton Anxiety Scale (HAMA) total score. Secondary measures included Visual Analogue Scales (VAS) for pain and Sheehan Disability Scale (SDS). Patients with baseline VAS overall pain severity score >30 were included in these analyses. National or institutional review boards at each study site approved the protocols, and all patients provided signed informed consent prior to study participation, in accordance with the Declaration of Helsinki. Results: In patients having baseline VAS score >30 (duloxetine N = 208, placebo N= 146), duloxetine-treated patients had significantly greater improvement compared with placebo-treated patients on anxiety symptoms as measured by the HAMA total score (P =.017), and on patient functioning as measured by the SDS Global Functional Impairment Score (P <.001) and across all SDS domains, including work/school (P =.001), social life (P <.001), and family/home management (P < .001). In the same group of patients, duloxetine-treated patients also demonstrated significantly greater improvements compared with placebo-treated patients on five of six VAS pain items: overall pain (P =.004), headache (P =.045), shoulder pain (P =.015), daily interference due to pain (P =.004), and the proportion of day while awake with pain (P =.011). Conclusion: These results suggest that in patients with GAD who present with clinically significant painful physical symptoms, duloxetine may be effective in reducing anxiety symptoms, pain severity, and in improving function.