OBJECTIVES Recognition and understanding of generalized anxiety disorder(GAD) have expanded in recent years. GAD is associated with high use of health care resources, predominantly primary care, and its economic burden on society is considerable. The objective of this study was to assess the cost-effectiveness of current treatments for GAD from the payer's perspective. METHODS We developed a micro-simulation model to estimate costs and effectiveness during a time horizon of 12 weeks. Effectiveness was assumed as the percentage of patients with complete response at the end of the follow-up period using the Hamilton Anxiety Rating Scale (HAM-A) –over 50% reduction related to baseline score- and Quality Adjusted Life Years (QALYs) gained. Model probabilities were obtained from a systematic review involving international published trials. Comparators used in the assessment were lorazepam (6mg/day); alprazolam (1.5mg/day); venlafaxine(75mg/day) and pregabalin(150-600mg/day). Resource use and costs were obtained by a panel of Mexican experts through the Delphi technique and official institutional databases. Costs include outpatient and inpatient services, drug, procedures, etc. The model was validated according to international guidelines. One-way and probabilistic sensitivity analyses were performed and acceptability curves were constructed. RESULTS Pregabalin had the highest percentage of patients with over 50% reduction on the HAM-A scale (64.7%); followed by venlafaxine(54.1%), lorazepam(40.8%) and alprazolam(38.2%). Regarding QALYs the highest results corresponded to pregabalin (0.1838QALYs); followed by venlafaxine (0.1787QALYs), alprazolam (0.1776QALYs) and lorazepam (0.1753QALYs). The 12-week expected mean costs per patient were US$1525.0±531.3; US$1532.6±548.3; US$1582.2±573.0 and US$1,635±604.6; respectively following the last order above. The ICER for pregabalin vs. venlafaxine(baseline) was US$465.7 for HAM-A and US$26,075.7 for QALYs. Pregabalin dominated lorazepam and alprazolam (p<0.05). First-order Monte Carlo sensitivity analyses showed results robustness and that pregabalin was the most cost-effective therapy using international thresholds. CONCLUSIONS Pregabalin showed to be a cost-effective and cost-saving therapy in the management of Mexican patients with GAD.