This double-blind, randomized, placebo-controlled trial evaluated efficacy and safety of pregabalin for management of FMS. Patients meeting ACR criteria and who had mean baseline pain score ≥4 (on an 11-point NRS) and pain VAS score ≥40 mm (0-100–mm scale) entered a 1-week, single-blind, placebo–run-in period. Those who had ≥30% reduction in VAS score during placebo run-in were discontinued. Other qualified patients were randomized to pregabalin 300, 450, or 600 mg/d (BID) or placebo for 14 weeks of treatment (2-week dosage escalation and 12-week fixed-dosage). Primary efficacy parameters were endpoint mean pain score (NRS from daily pain diary), PGIC, and Fibromyalgia Impact Questionnaire (FIQ). 745 patients were randomized: 95% were female, mean age=50 years, median FMS duration=8 years, baseline mean pain score=6.7. 486 (65%) completed the trial. Pregabalin significantly improved pain: differences from placebo in mean change from baseline to endpoint in mean pain score were, 300 mg/d, 0.71 (P=.0009); 450 mg/d, -0.98, and 600 mg/d, -1.00 (each P<.0001). Significantly greater proportions of patients responded (≥30% improvement) to pregabalin than placebo: 300, 42% (P=.0172); 450, 50% (P=.0002); 600 mg/d, 48% (P=.0006); placebo, 30%. Significant changes in mean pain score were evident as early as Week 1 and were sustained to endpoint. On the PGIC, there was statistically significant improvement for all pregabalin groups compared with placebo, with 68% of 300-, 78% of 450-, and 66% of 600-mg/d patients reporting at least minimal improvement vs 48% of placebo. On the FIQ, patients in the 450- and 600-mg/d groups showed statistically significant improvement vs placebo (treatment differences: 450 mg/d, -5.24, P=.0041; 600 mg/d, -5.34, P=.0034). The most common AEs were dizziness (all pregabalin, 35.8%; placebo, 7.6%) and somnolence (18.0%; 3.8%). Pregabalin, at all dosages, demonstrated rapid and sustained pain relief and at 450 and 600 mg/d demonstrated effective management of FMS.