OBJECTIVES: Quantify the cost effectiveness of treatments for macular edema (ME) secondary to branch or central retinal vein occlusion (BRVO, CRVO) from U.S. payer/societal perspectives. METHODS: A Markov model consisting of five visual acuity (VA) health states and death was developed to quantify clinical outcomes, costs, and quality-adjusted life-years (QALYs) associated with no treatment (observation) or two-year treatment with ranibizumab monotherapy (six monthly injections; as needed thereafter), laser photocoagulation (BRVO only), ranibizumab plus laser (BRVO only), triamciniolone acetonide (CRVO only), or dexamethasone intravitreal implant. Transition probabilities were based on patient-level data for ranibizumab (± laser) and published literature for the remaining alternatives. Health state-specific costs and utilities were accrued for 13 years—approximate median survival of an RVO patient—with costs and QALYs discounted 3% annually. Costs associated with treatment, adverse events, and impaired vision were expressed in 2011 U.S. dollars. Incremental cost-effectiveness ratios (ICERs) were calculated comparing the least costly alternative to the next most costly strategy. Deterministic and probabilistic sensitivity analyses were conducted.   RESULTS: Ranibizumab demonstrated superior efficacy relative to other strategies in both BRVO and CRVO but was most costly ($26,732 and $32,850; BRVO and CRVO, respectively). Other strategy costs ranged from $10,622 (observation in BRVO) to $16,090 (dexamethasone intravitreal implant in CRVO patients). QALYs were greatest for ranibizumab (6.75 and 6.10; BRVO and CRVO, respectively) compared to a range of 4.88 (observation in CRVO) to 5.93 (laser in BRVO). Dexamethasone intravitreal implant was dominated in BRVO as was no treatment in CRVO. ICERs for ranibizumab were favorable ($19,270/QALY vs laser in BRVO; $34,204/QALY vs dexamethasone intravitreal implant in CRVO). At a threshold of $50,000/QALY, probabilistic analyses suggested ranibizumab to be cost effective in 99.7% (BRVO) and 88.3% (CRVO) of simulations. CONCLUSIONS: In patients with ME secondary to BRVO or CRVO, ranibizumab is a cost-effective treatment alternative.