OBJECTIVES: To calculate the cost-effectiveness of ranibizumab versus licensed comparators in wet age-related macular degeneration (AMD) from a French societal perspective based on real-life observational data. METHODS: A Markov model was developed containing 5 health states defined by visual acuity (VA) of the treated eye and a death state. The model time horizon covered 2 years of treatment followed by 8 years of best supportive care (BSC). Medical and non-medical resource use and efficacy during treatment were based on observational patient-level data with ranibizumab (LUEUR and LUMIERE studies) or verteporfin (OPV study). No observational data were available for pegaptanib. Efficacy was obtained per VA level to control for population differences in baseline VA. The base-case analysis reflects 1st line therapy. Mutual to both comparators, BSC was modelled with clinical trial placebo data and resource use estimates. Annual discount rates were 4% for costs (€ 2011) and outcomes. Utilities reflected general population preference (UK) using time-trade-off methods. RESULTS: Compared to verteporfin, 1st line ranibizumab provided a gain of 0.20 QALYs and avoided 0.63 years of vision impairment (YVI). The total incremental cost was €3,843. The cost-utility was €19,088/QALY, the cost per YVI avoided was €6,114. Similar outcomes were obtained when including pre-treated patients.  Ranibizumab was cost-effective with a probability of 62.8% and 78.2% at willingness to pay thresholds of €20,000/QALY and €30,000/QALY respectively. CONCLUSIONS: Based on real-life observational studies, 2-year treatment with ranibizumab was associated with improved vision-related health outcomes and a cost-utility ratio below commonly applied willingness to pay thresholds.