BACKGROUND: The aim of this study is to determine the most cost-effective strategy for the treatment of primary open-angle glaucoma (POAG) in Brazil, from the payer's perspective (Brazilian Public Health System) in the setting of the Glaucoma Referral Centers. METHODS: Study design was a cost-effectiveness analysis of different treatment strategies for POAG. We developed 3 Markov models (one for each glaucoma stage: early, moderate and advanced), using a hypothetical cohort of POAG patients, from the perspective of the Brazilian Public Health System (SUS) and a horizon of the average life expectancy of the Brazilian population. Different strategies were tested according to disease severity. For early glaucoma, we compared observation, laser and medications. For moderate glaucoma, medications, laser and surgery. For advanced glaucoma, medications and surgery. Main outcome measures were ICER (incremental cost-effectiveness ratio), medical direct costs and QALY (quality-adjusted life year). RESULTS: In early glaucoma, both laser and medical treatment were cost-effective (ICERs of initial laser and initial medical treatment over observation only, were R$ 2,811.39/QALY and R$ 3,450.47/QALY). Compared to observation strategy, the two alternatives have provided significant gains in quality of life. In moderate glaucoma population, medical treatment presented the highest costs among treatment strategies. Both laser and surgery were highly cost-effective in this group. For advanced glaucoma, both tested strategies were cost-effective. Starting age had a great impact on results in all studied groups. Initiating glaucoma therapy using laser or surgery were more cost-effective, the younger the patient. CONCLUSION: All tested treatment strategies for glaucoma provided real gains in quality of life and were cost-effective. However, according to the disease severity, not all strategies provided the same cost-effectiveness profile. Based on our findings, there should be a preferred strategy for each glaucoma stage, according to a cost-effectiveness ratio ranking.