BACKGROUND: Fibromyalgia is a chronic condition associated with widespread pain, sleep disturbance and disability. Disease related costs are high and effective treatment options few. OBJECTIVES: To evaluate the cost effectiveness of pregabalin in the treatment of fibromyalgia. METHODS: A decision-analytic model was developed comparing pregabalin 300 mg or 450 mg against placebo, duloxetine 60 mg or 120 mg, gabapentin, tramadol and amitriptyline. After a 12 week treatment phase patients who responded to treatment entered an ongoing treatment phase using a Markov model in which patients maintained response, lost response or dropped out. The base case considered patients with severe fibromyalgia defined as a Fibromyalgia Impact Questionnaire score of >or=59 and a pain score of >or=6.5 at baseline. Response rates for pregabalin and placebo were taken from three randomised trials, and a 1 year open-label extension study was used for long-term parameters. Response was defined as a >or=30% improvement over baseline in pain score and a patient global impression of change rating of much improved or very much improved. Relative rates of response for other comparators over placebo were extracted from a systematic review of published randomised controlled studies. The primary effectiveness endpoint was Quality Adjusted Life Years (QALYs). Utilities gained over baseline were estimated by applying the SF-6D utility algorithm to SF-36 data collected in the pregabalin trials. Resource use associated with fibromyalgia management was estimated from published studies and costs were estimated from the UK NHS perspective at 2008 prices. Costs and QALYs were discounted at 3.5%. Non-parametric bootstrapping analysis was used to generate confidence intervals. RESULTS: In the base case, pregabalin 300 mg and 450 mg increased cost per patient by pound601 (95% CI: 532, 669) and pound653 (587, 727) and improved QALYs per patient by 0.03 (-0.03, 0.06) and 0.03 (-0.04, 0.08) respectively compared to placebo. The cost per QALY gained (CQG) was pound23,166 and pound22,533. In the base case population CQG for pregabalin 450 mg against duloxetine 60 mg and 120 mg was pound19,224 and pound14,096, against gabapentin pound35,737, against tramadol pound98,072, and was dominated by amitriptyline. Sensitivity analysis found the cost effectiveness of pregabalin to be most sensitive to drug price and response rates. Limitations of the analysis include different definitions of response used and lack of subgroup data reported in the published studies synthesised, and limited data on long-term effect of therapies in fibromyalgia. Although the analysis was based on the best available evidence, the comparisons against amitriptyline and tramadol rely on old studies that were not designed to meet current quality criteria. CONCLUSION: This model found pregabalin 300 mg and 450 mg to be cost effective compared with placebo and, within the limits of available evidence, against duloxetine using standard UK criteria in patients with fibromyalgia experiencing severe pain.