OBJECTIVES To estimate the cost-effectiveness of ranibizumab 0.5mg pro re nata (PRN) compared with aflibercept 2mg bi-monthly in the treatment of visual impairment (VI) due to diabetic macular oedema (DMO) taking a UK healthcare perspective.  METHODS A Markov model previously reviewed by the National Institute for Health and Care Excellence (NICE) was used to simulate the long-term outcomes and costs (at 2012 price level) of treating DMO. The health states were defined by increments of 10 letters in best-corrected visual acuity (BCVA) with a 3-month cycle length. Patients could gain (or lose), at most, 2 health states between two cycles. A lifetime time horizon was implemented. Future costs and health outcomes were discounted at 3.5% per annum. Baseline characteristics, ranibizumab effectiveness and adverse events were estimated with data from the RESTORE trial (36 months). A published network meta-analysis was used to assess the relative effectiveness of ranibizumab to aflibercept. Aflibercept injection frequency was calculated with VIVID/VISTA phase III trials. Different utilities were used if the treated eye was the better or the worse-seeing eye. RESULTS Ranibizumab monotherapy leads to an incremental gain of 0.05 quality-adjusted life-years (QALY) (0.04 from the better-seeing eye and 0.01 from the worse-seeing eye) with a cost savings of ₤5,841 relative to aflibercept. Therefore, ranibizumab provides greater health gains with lower overall costs than aflibercept. Probabilistic sensitivity analysis shows that ranibizumab has a 58% probability of being dominant and 79% probability of being cost effective compared with aflibercept at a willingness-to-pay threshold of £20 000/QALY. CONCLUSIONS Ranibizumab is dominant over aflibercept in the treatment of VI due to DMO.