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Background Diabetic retinopathy (DR) is a leading cause of preventable blindness among people with type 2 diabetes mellitus (T2DM). Early detection is essential to prevent vision-threatening complications. This study evaluated the long-term cost-effectiveness of CODMAP (Ophthalmologic Screening for Diabetes Mellitus in Primary Care (Cribado Oftalmológico en Diabetes Mellitus en Atención Primaria)), an optimised screening programme combining two-field non-mydriatic fundus photography (NMFP) and optical coherence tomography versus conventional single-field NMFP in a public healthcare setting.Methods A Markov model simulated DR progression over 50 years in a cohort of 7729 patients with T2DM. Eight health states reflected DR severity, with state-specific costs and quality-adjusted life years (QALYs) accrued annually. Analyses took the perspective of the Spanish National Health Service, applying a 3% annual discount rate. Incremental cost-effectiveness ratios, calculated as a ratio of means (ICERs ROM), and net monetary benefits (NMBs) were estimated through 10 000 Monte Carlo simulations, at a €30 000 willingness-to-pay threshold. Deterministic and probabilistic sensitivity analyses, scenario analyses and bootstrap validation were performed.Results CODMAP accrued higher costs (€206.4 million vs €205.1 million) but more QALYs (128 691.7 vs 118 013.8), resulting in an ICER ROM of €124.25/QALY. The probability of cost-effectiveness at €30 000/QALY was 74.3%, remaining stable in scenario analyses (75.7%–78.8%). Mean incremental NMB in the base case was €319.0 million. Cost and QALY variations were the main drivers of uncertainty.Conclusion CODMAP offers greater long-term health gains at a favourable incremental cost per QALY in the Spanish context. However, the non-definitive probability of cost-effectiveness warrants cautious policy consideration, with attention to local infrastructure, implementation capacity and cost structures.