OBJECTIVES: Diabetic retinopathy/ DME are substantial complications leading to blindness. Ranibizumab (RBZ) 0.5mg and aflibercept (ABC) (anti-VEGF) change the DME-treatment paradigm. We estimated the cost-effectiveness of RBZ vs. ABC and laser from the Czech health care system perspective. METHODS: A Markov cohort model with 8 health states (based on visual acuity) + dead in life-time horizon (3% discount rate) was used. Base-line patient characteristics came from the RESTORE study; 60% of patients were treated for their worse seeing-eye. Patients who were treated in both eyes were not included in the analysis. Transition probabilities (efficacy) for the first 3 years of treatment for RBZ 0.5mg and laser were derived from RESTORE, for ABC from a published network meta-analysis (gain at least 10 letters: RBZ vs. ABC: OR = 1.59; 95%CrI 0.61 – 5.37). Natural progression of disease came from Wisconsin Epidemiologic Study. Utility for better and worse seeing-eye were derived from literature. RBZ and ABC dosing came from RESTORE (pro re nata, PRN) and from VIVID-DME, VISTA-DME study (bi-monthly after 5 initial monthly doses), respectively. Cost parity per dose of anti-VEGF (€855) was assumed. RESULTS: Using a life-time horizon, total (discounted) costs and QALYs for RBZ, ABC, laser were: €7,110; €9,562; €1.490 and 7.589; 7.502; 7.022 QALYs, respectively. The incremental costs and QALYs for RBZ vs. laser were €5.620 and 0.567 QALYs, with base-case ICER of 9.918 €/QALY. RBZ vs. ABC brought 0.087 QALY gain with €2.452 savings, reflecting dominance of RBZ over ABC. According to probabilistic sensitivity analysis, there is 64%/ 90% probability that RBZ’s ICER is below 1GDP/ 3GDP per capita (€13,800/ €40,000) compared to laser. There is 62% probability that RBZ compared to ABC brings more QALY with lower costs. CONCLUSIONS: RBZ is dominant, cost-effective compared to ABC, laser approach, respectively in DME patients from the Czech health care system perspective.