OBJECTIVES Patients with fibromyalgia (FM), a major cause of morbidity, use health services extensively and have an estimated prevalence of 3.4% for women and 0.5% for men. The aim of this study was to assess the cost-effectiveness of pregabalin in the treatment of FM from the health care payer's perspective. METHODS We developed a three-state Markov model to simulate health and economic outcomes during a time horizon of one-year (12-week cycles). The model includes several stages related to functional disability (mild-pain, moderate-pain and severe-pain). Effectiveness was assumed as the percentage of patients with no or mild pain (pain score<4) at the end of the follow-up period using a Visual Analogue Scale(VAS). Transition probabilities were obtained from a systematic review involving national and international published trials. Comparators used in the assessment were amitriptyline (25-50mg/day); pregabalin (150-450mg/day); fluoxetine (20-80mg/day); duloxetine (60-120mg/day); gabapentin(300-1200mg/day); tramadol(150-1300mg/day)+acetaminophen(325-2600mg/day) and fluoxetine(20-80mg/day)+amitriptyline(10-50mg/day). Resource use and costs were obtained from 5000 randomized hospital records from the Social Security Mexican Institute(IMSS) and official institutional databases. Costs include outpatient and inpatient services, drug, procedures, etc. The model was validated according to international guidelines. Probabilistic sensitivity analyses were performed employing bootstrapping techniques and acceptability curves were constructed. RESULTS The highest percentage of patients with no or mild pain during the follow-up period was obtained by pregabalin(44.8%; CI95% 42.8%-48.0%); followed by gabapentin(38.1%; CI95% 33.2%-43.5%); duloxetine(34.2%; CI95% 27.8%-40.6%) and amitriptyline(22.2%; CI95% 21.0%-24.0%).The annual expected mean costs per patient were US$1503.2(US$1472.2-US$1534.09); US$1,742.7(US$1,715.1-US$1,770.2); US$2,046.6(US$2018.6-US$2074.7) and US$643.6(US$615.2-US$673.5), respectively. The ICER of pregabalin vs. amitriptyline(basecase) was US$3798.9(US$3336.1-US$4,325.9). Other treatments were dominated by pregabalin. Second-order Monte Carlo sensitivity analyses indicated that pregabalin would be a cost-saving strategy in a range of 60%-70% within accepted thresholds(p<0.05). CONCLUSIONS In Mexico, pregabalin showed to be a cost-effective and cost-saving therapy when compared with amitriptyline and other usual treatments in the management of FM.