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To investigate the long-time visual outcome in patients with diabetic macular edema treated with ranibizumab in an ordinary clinical setting.One hundred two eyes of 80 patients were followed for 4 years. All patients received a loading dose of 3 monthly ranibizumab 0.5-mg injections. From Month 3 to Month 48, patients received ranibizumab reinjections pro re nata based on disease activity.Excluding deaths, the 4-year visit was completed by 82% of the study eyes. The best-corrected visual acuity improved by 6.6 Early Treatment Diabetic Retinopathy Study letters at 4 years (P < 0.001). The patients received a mean of 7.7 ± 3.4 ranibizumab injections for 4 years. The number of injections (mean ± SD) given were 4.7 (1.1), 1.4 (1.4), 0.7 (1.1), and 0.9 (1.4) during Years 1 to 4, respectively. No difference in the injections needed was seen between patients who had previously received focal/grid laser and treatment-naive subjects.The gain in the best-corrected visual acuity achieved after the initial loading dose was sustained over time with a pro re nata regimen. The number of injections needed to maintain the best-corrected visual acuity was low during the study period.