Objective: To assess the cost-effectiveness of pregabalin in the treatment of fibromyalgia (FM) from a US perspective. Methods: We developed a micro-simulation model to assess the cost-effectiveness of pregabalin therapy (450 mg/d) in a hypothetical cohort of patients with moderate or worse pain due to FM. The model simulates pain experience on a weekly basis over 14 weeks, using data from a randomized, placebo-controlled clinical trial. Pain levels were estimated using an 11-point numeric rating scale; moderate or worse pain was assumed to be a pain score ³4. Health-state utilities were assigned based on estimated pain level, using published values for the Health Utilities Index [HUI] - Mark II. Costs of drug therapy only were considered. Cost-effectiveness of pregabalin therapy was considered alternatively versus placebo and no therapy, the latter because pregabalin is the only drug currently indicated for the treatment of FM. Cost-effectiveness was expressed in terms of both incremental cost per additional day without moderate or worse pain and incremental cost per quality-adjusted life-year (QALY) gained. Results: In comparison with no treatment, pregabalin therapy was estimated to yield an average of 29.4 additional days without moderate or worse pain over 14 weeks, and a gain of 0.019 QALYs. Corresponding estimates for the comparison with placebo were 11.4 additional days without moderate or worse pain, and 0.009 additional QALYs. Assuming a daily cost of therapy of $3.30, the incremental cost (95% CI) of pregabalin therapy per additional day without moderate or worse pain was $11 ($9, $14) versus no treatment, and $32 ($18, $72) versus placebo. Corresponding estimates of the incremental cost per QALY gained were $39,266 ($27,167, $57,269) and $17,220 ($15,289, $20,153), respectively. Conclusion: In patients with moderate or worse pain due to FM, the cost-effectiveness of pregabalin falls within accepted published thresholds.