OBJECTIVES: To assess the cost-utility of intravitreal treatment with ranibizumab (Lucentis) versus current management of wet subfoveal age-related macular degeneration (AMD) from the perspective of the Belgian health care payer (RIZIV/INAMI + patient) and social security. METHODS: A 10-year Markov model was developed containing 5 disease states defined by treated eye visual acuity (VA) and a state “death”. AMD lesion types included minimally classic (MC-AMD), occult (OC-AMD) and predominantly classic (PC-AMD). Safety and VA transition probabilities were obtained form phase III clinical trials (MARINA, ANCHOR, PIER). In the base-case, the model simulates the clinical trial treatment durations of 1 year (PC-AMD) and two years (MC-AMD, OC-AMD). Treatment was followed by best supportive care (BSC). Ranibizumab PRN dosing was modeled as 8 and 6 annual injections over the first 2 years. Ranibizumab was compared to verteporfin + photodynamic therapy (V+PDT) in PC-AMD and OC-AMD and to BSC in all lesions. National age-adjusted mortality was applied. Direct medical costs were calculated by multiplying resource use obtained through expert opinion with unit costs. Direct non-medical costs of blindness were derived from literature. Utility scores were obtained from a general population sample using time-trade-off methodology. Costs were discounted at 3% annually, effects at 1.5%. Univariate and probabilistic sensitivity analyses were performed. RESULTS: In the base-case analysis, ranibizumab was cost-effective in all lesions. The probability of incremental cost-utility below 35,000€/QALY was 98% in PC-AMD, 83% in OC-AMD and 79% in MC-AMD. Sensitivity analyses ranged from dominance for 1 year treatment in PC-AMD to 36,755€/QALY for 3 years treatment (4 injections in 3rd year) in OC-AMD. Results were sensitive to ranibizumab dosing frequency and duration and to the cost of blindness. CONCLUSION: PRN dosing of ranibizumab for one to three years was cost-effective in all lesion types, from a health care payers and social security perspective.