Objective. Irritable bowel syndrome (IBS) is commonly comorbid with generalized anxiety disorder (GAD). We evaluated whether duloxetine would lead to improvement in symptoms and quality of life in patients with both conditions. Method. A 12-week, open-label trial of duloxetine was conducted in 13 subjects with IBS and GAD. The primary outcome measure was the Clinical Global Impression (CGI) Scale. Secondary measures included the Hamilton Anxiety Rating Scale, IBS Quality of Life (IBS-QOL) Scale, and IBS Symptom Severity Scale (IBS-SSS). Results. Repeated measures ANOVA was used to examine the effect of treatment with duloxetine on ratings of anxiety and IBS. Significant improvement was observed on the CGI-Improvement (F = 14.19, df = 1,12, p < 0.001) and Severity scales (F = 16.16, df = 1,12, p < 0.001). Secondary measures revealed significant reduction in symptoms of anxiety (F = 11.66, df = 1,12, p < 0.01), eta(2)(p) = 0.56, and IBS-SSS (F = 6.05, df = 1,12, p < 0.001), eta(2)(p) = 0.34, in addition to IBS-QOL improvements (F = 11.66, df = 1,12, p < 0.01), eta(2)(p) = 0.56. Conclusion. Results of this pilot study support the efficacious use of duloxetine in comorbid IBS and GAD. Participants reported significant reductions in IBS components, as well as improvement in GAD.