OBJECTIVES: Fibromyalgia (FM) is a disease with a great economic impact not only related to the costs associated but also to the loss of productivity. Effective treatment options in the Mexican market are few. The objective of the present analysis is to assess the cost-effectiveness of duloxetine in the treatment of patients with FM versus pregabalin. METHODS: Alternatives to compare were: (1) duloxetine 60 mg / day and 120 mg / day and (2) pregabalin 300 mg / day and 450 mg / day.  A decision tree model was developed with a 12 weeks time horizon in which patients maintained response, lost response or dropped out. Relative rates of response for other comparators over placebo were extracted from a systematic review of published randomized controlled studies for achieving a reduction of 30% in the Brief Pain Inventory average pain severity score or a “much improved” or “very much improved” rate in the Patient Global Impression of Improvement (PGI). Resource use associated with fibromyalgia management was estimated from published studies and costs were estimated from the Mexican Public Healthcare Payer perspective at 2010 USD prices. RESULTS: In the base case duloxetine 60 mg/day versus the two indications of pregabalin were compared considering the price per milligram for the 14 and 28 tablets of 75 mg presentations of pregabalin. In this case, duloxetine is a dominant strategy versus pregabalin in 3 out of four scenarios and highly cost-effective when compared duloxetine 120mg/day versus pregabalin 300mg/day. Further analysis (considering presentation 14/28 tablets of 150 mg of pregabalin), shows that duloxetine is a highly cost-effective alternative with cost-effectiveness ratios of $34-405 USD range per one additional response. CONCLUSIONS: Results suggest duloxetine is a dominant and highly cost-effective alternative compared with pregabalin at therapeutic doses published in studies of comparable design in patients with FM.