We report on a trial (FREEDOM) designed to evaluate pregabalin for durability of effect in reducing pain associated with FMS. This placebo-controlled, double-blind study consisted of a 1-week screening phase; a 6-week open-label phase (individualized dosage optimization to 300, 450, or 600 mg/d); and a 26-week double-blind phase. Patients who had ≥50% reduction in mean pain VAS score from open-label baseline and scored "much improved" or "very much improved" on the PGIC at 2 of the final 3 visits in open-label were eligible for randomization to placebo or their optimal dosage of pregabalin. The primary endpoint of the double-blind phase was time to loss of therapeutic response (LTR), defined as <30% reduction in pain VAS score (from open-label baseline) during 2 consecutive visits or subjective worsening of FMS symptoms. 6 sensitivity analyses--using alternative definitions of LTR based on different assumptions about censored patients--were performed. 1051 patients entered open-label: 93% were female, 88% were white; mean age=50 years, FMS median duration=7.8 years, baseline mean pain VAS score=78 mm. 663 patients completed open-label; 566 were randomized: 279 to pregabalin, 287 to placebo. Time to LTR was significantly longer for pregabalin vs placebo (P<.0001): 25% of placebo patients had LTR by Day 7, compared with Day 34 for pregabalin patients. Nearly twice as many placebo patients (174; 61%) had LTR by end of double-blind vs pregabalin patients (90; 32%). All 6 sensitivity analyses confirmed the robustness of these findings: in each analysis, time to LTR was significantly longer for pregabalin vs placebo (P<.0001). Dizziness (36%) and somnolence (22%) were the most common treatment-associated AEs during open-label. In double-blind, the most common AEs exceeding placebo were sinusitis (5% vs 3%), arthralgia and anxiety (5% vs 2%). Pregabalin significantly delayed time to LTR, demonstrating durability of maintaining pain reduction in patients with FMS.