OBJECTIVES:  Fibromyalgia (FM) is a chronic condition characterized by widespread pain and can impose substantial economic burden. This study estimates the annualized differences in healthcare costs associated with improvement in FM severity among pregabalin-treated patients. METHODS: Data from 3 similarly designed, 3-month placebo-controlled, clinical trials of pregabalin in FM patients were modeled. Extrapolation of efficacy results was based on a 1-year open-label study. Mean annual costs (direct and indirect) were assigned based on FM severity levels (mild: $10,219; moderate: $26,217; severe: $42,456) and were derived from the US Fibromyalgia Burden of Illness Study. FM severity levels were defined using established cutpoints on the Fibromyalgia Impact Questionnaire. Mean annualized costs at endpoint were estimated for all patients within each cohort and the mean differences in costs were compared between cohorts using a regression model. RESULTS: Relative to placebo, the proportion of mild subjects at endpoint was significantly higher with pregabalin 450mg and significantly lower for severe subjects. Mean total costs were lower with pregabalin (300mg, $25,721; 450mg, $24,103) than placebo ($26,162). Relative to placebo, the difference in mean annual costs was $2059 lower for pregabalin 450mg (P=0.003) and $441 lower for pregabalin 300mg (P=0.52). Mean direct costs were higher with pregabalin (300mg, $4,962; 450mg, $4820) than placebo ($4,364). Relative to placebo, the difference in mean annual direct costs was significantly higher for pregabalin 450mg by $456 (P<0.0001) and by $599 for pregabalin 300mg (P<0.0001). Mean indirect costs for pregabalin (300mg, $20,783; 450mg, $19,306) were lower than placebo ($21,735). Relative to placebo, the difference in mean annual direct costs for pregabalin 450mg was significantly lower by $2,429 (P<0.0001), and for pregabalin 300mg was lower by $951 (P=0.12). CONCLUSIONS: Improvements in FM severity are associated with overall reductions in costs that may offset the costs of treatment with pregabalin.