Introduction: Information about real-world ranibizumab use is needed to optimize treatment of macular edema secondary to retinal vein occlusion (RVO). The BOREAL-RVO study assessed treatment use, effectiveness and safety of 24-month treatment with ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to RVO in a real-world setting. Methods: This was a multicenter, post-authorization, observational study in France, including patients starting ranibizumab for RVO. Primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at Month 6. Secondary endpoints were mean changes from baseline in BCVA at Month 24 and central retinal thickness (CRT) at Months 6 and 24, and treatment use in real-world setting. Results: 226 branch RVO (BRVO) and 196 central RVO (CRVO) patients were enrolled; 71.7% and 70.9% completed the 24-month follow-up, respectively. In BRVO, mean (SD) baseline BCVA was 55.2 (18.7) letters, with gains of 14.3 (13.7), 14.1 (16.5), 13.0 (17.5) and 11.4 (20.1) letters at Months 3, 6, 12 and 24. In CRVO, mean (SD) baseline BCVA was 40.4 (25.6) letters, with gains of 16.0 (21.2), 9.5 (25.4), 9.2 (27.7) and 8.3 (23.8) letters at Months 3, 6, 12 and 24. At Month 24, 52% of BRVO and 41% of CRVO patients had gains of 15 or more letters. In BRVO, mean (SD) CRT values at baseline and Months 3, 6, 12 and 24 were 550 (175), 315 (104), 343 (122), 335 (137) and 340 (105) μm. In CRVO, mean (SD) CRT values at baseline and Months 3, 6, 12 and 24 were 643 (217), 327 (152), 400 (203), 379 (175) and 348 (161) μm. On average, BRVO patients had 3.8 injections for 6.9 visits by Month 6, and 7.2 injections for 19.7 visits by Month 24. CRVO patients had 2.7 injections for 4.2 visits by Month 6, and 7.1 injections for 21.1 visits by Month 24. Factors predictive of better BCVA gain at Month 6 were age under 60 at baseline, lower baseline BCVA and BCVA gain at Month 3. There were no new safety findings. Conclusion: Major improvements in BCVA and CRT were observed at Month 3 after the induction phase, and then was sustained up to Month 24, with a slight decrease, probably due to under-treatment. This study demonstrated ranibizumab to be a safe and effective treatment for BRVO and CRVO in the real-world setting, although more regular or pro-active treatment could further improve outcomes.