BACKGROUND: To assess the efficacy (in particular, in pain, functional impairment, and quality of life) and safety and tolerability (incidence of adverse events, discontinuation rates, changes in laboratory findings, and vital signs) of duloxetine in female patients with fibromyalgia. METHODS: Data were pooled from two placebo-controlled clinical trials of similar design (randomized, 12-week, and double-blind), comparing duloxetine 60 mg a day (q.d.) or 60 mg twice daily (b.i.d.) (n = 326) with placebo (n = 212), in women who met the American College of Rheumatology criteria for primary fibromyalgia. RESULTS: Compared with the patients receiving placebo, duloxetine-treated female patients demonstrated a significantly greater improvement in the Brief Pain Inventory (BPI) average pain severity score and in the Fibromyalgia Impact Questionnaire (FIQ) total score, beginning at week 1 and continuing through week 12 (p < 0.001). Duloxetine was superior to placebo on all efficacy measures, including mean tender point threshold, Clinical Global Impression of Severity, Patient Global Impression of Improvement, and average interference from pain scores. The duloxetine-treated group was superior to placebo on all quality of life and functional measures, including each domain of the Medical Outcomes Study Short Form-36 (SF-36). A direct treatment effect of duloxetine on pain reduction was demonstrated and shown to be independent of secondary improvement in mood (based on BPI average pain score). Significantly more duloxetine-treated patients reported treatment-emergent adverse events (296 [90.8%] duloxetine-treated and 165 [77.8%] placebo-treated, p < 0.001). Rates of serious adverse events were similar between duloxetine-treated and placebo-treated patients. CONCLUSIONS: The pooled results of these studies demonstrate that duloxetine is a safe and efficacious treatment for both the pain and functional impairment associated with fibromyalgia in female patients, while significantly improving quality of life.