Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.