BACKGROUND: Osteoarthritis (OA) is the most common rheumatic disease in the world and one of the main causes of joint pain and disability of the adult population; it therefore represents an important use of medical resources for the institutions and compromises the quality of life of patients. OBJECTIVES: To analyze the cost-effectiveness of Bio-HA vs. Hilano G-F20 in patients with knee osteoarthritis. METHODS: We conducted an economic evaluation. The alternatives to compare were Bio-HA vs Hilano, administered three weekly injections, with follow-up evaluations at week 12. The perspective is the Mexican Social Security Institute (IMSS). The economic model included the cost of drug acquisition and management of adverse events (AE). The use of resources associated with each AE was defined according to a Delphi Panel. The efficacy measure was the proportion of patients with OMERACT-OARSI response, obtained from a head to head analysis (Onel E, 2008). RESULTS: The response rates for Bio-HA were 71% versus 63% for Hilano. The knee effusions in patients treated with Bio-HA was 0.6% (MX$39) vs. Hilano 8.1% (MX$531). The cost per patient treated for each alternative was MX$7728 and MX$8338 for Bio-HA and Hilano, respectively. The cost per responder patient was lower for Bio-HA than Hilano, MX $10,885 and MX $13,236, respectively. So, the savings generated by Bio-HA are very high. If we consider the 1,000 patients for each alternative, the savings would be MX$610,000 and this money be useful to purchase an extra 122 cycles of treatment with Bio-HA or to be reassign for other therapeutic areas. Considering all the above Bio-HA proved to be a dominant strategy (less costly and more effective). CONCLUSIONS: The results of this pharmacoeconomic analysis suggest that the use of Bio-HA in patients with OA is a cost-saving strategy for the institutions of public health in Mexico.