OBJECTIVES: Fibromyalgia is a chronic condition manifesting with widespread pain, non-restorative sleep, fatigue and cognitive dysfunction. Fibromyalgia imposes high costs due to work loss and medical resource use. We built a decision-analytic model to assess the cost-effectiveness of treating severe fibromyalgia with pregabalin. METHODS: Patients considered had Fibromyalgia Impact Questionnaire scores>59 and pain scores>6.5 at baseline. Pregabalin 450mg and 300mg were compared to placebo, duloxetine, gabapentin, tramadol, milnacipran and amitriptyline. Patient response was assessed after 12 weeks of therapy: responders entered a long term model in which they maintained response, lost response, or dropped out. Response rates for pregabalin and placebo were derived from a pooled analysis of 3 randomized trials: response was defined as a ≥30% improvement over baseline pain score and patient global impression of change rated much or very much improved. Response rates for other comparators were obtained from a systematic review of randomized controlled studies. Longer term outcomes were derived from an open-label follow-up extension of a randomised pregabalin study. The primary effectiveness endpoint was mean days in response. Resource use was estimated from published studies. Costs were calculated from a societal perspective including health care costs and productivity loss. RESULTS: At 12 weeks, people treated with pregabalin achieved 28 days in response compared to 14 with placebo. Total cost per patient was $402 higher with pregabalin 300mg and $989 lower with pregabalin 450mg compared to placebo. At 1 year, pregabalin 300mg was less costly and more effective than placebo, duloxetine, milnacipran or gabapentin: the incremental cost per additional day in response compared to tramadol and amitriptyline was $43 and $10 respectively. Pregabalin 450mg gave reduced costs and more response days than all comparators.  CONCLUSIONS: Pregabalin was found to be an effective therapy for severe fibromyalgia patients and was cost-saving compared to most other fibromyalgia treatments.