OBJECTIVES: To assess whether evidence-based cost-utility of PRN-dosing with ranibizumab (Lucentis®, RBZ-PRN) in age-related macular degeneration (AMD) is comparable to RBZ-PRN cost-utility estimated previously based on clinical data from monthly and quarterly regimens. METHODS: A 10-year MS-Excel Markov model with 5 visual acuity (VA) levels and 1 death state predicts VA in patients treated with RBZ-PRN, RBZ quarterly (RBZ-Q), RBZ monthly (RBZ-M), Visudyne® photodynamic therapy (PDT) or best supportive care (BSC). Transition probabilities, adverse events and treatment frequencies were provided by newly available PRN-trials (SUSTAIN, MONT BLANC) + available trials covering other comparators (ANCHOR, MARINA, PIER, EXCITE, TAP). Comparability of populations and treatment effects (linear regressions) determined trial data pooling. Final analyses included pooled datasets (RBZ-PRN and RBZ-Q) or multiple single-trial datasets (other comparators). Secondary analysis included indirect comparison versus pegaptanib sodium (PGB). Two-year treatment duration was followed by BSC. Costs (2009, UK health care payer, 3.5% discount) were obtained from literature and expert opinion; utilities (3.5% discount) from a time-trade-off study. One-way and probabilistic sensitivity analyses (SA) covered variability in efficacy, costs, treatment frequency and utilities. RESULTS: Due to lower than predicted injection frequency, clinical trial-based cost-utility of RBZ-PRN was better than predicted cost-utility. Evidence-based cost-utility ranged from £4,414/QALY to £20,489/QALY versus BSC and from dominance to £2,383/QALY versus PDT. RBZ-PRN was dominant versus RBZ-Q and versus PGB (secondary indirect analysis). RBZ-M was slightly more effective but not cost-effective versus RBZ-PRN. The result was most sensitive to time horizon (2-10y), cost of blindness and treatment duration (1-3y) but conclusions remained throughout 1-way SA. Assuming a threshold of £30,000/QALY, the probability that RBZ-PRN is cost-effective ranged from 68% to 97% versus different comparators. CONCLUSIONS: RBZ-PRN using the SUSTAIN and MONT-BLANC re-treatment criteria is cost-effective compared to other therapies for wet-AMD and represents the most cost-effective use of RBZ.