Background: The complement component 5 inhibitor therapies (C5ITs) eculizumab and ravulizumab have been approved or submitted for regulatory approval in several regions for AQP4+ NMOSD. Methods: This global, long-term, prospective, multicenter, observational registry will enroll adult patients with AQP4+ NMOSD being treated with eculizumab or ravulizumab and who have received ≥1 dose of eculizumab or ravulizumab within 4 or 12 weeks prior to enrollment, respectively. Inclusion criteria include available historical data on C5IT dosing since initiation and the number and types of relapses from 1 year prior to C5IT initiation through enrollment. The primary outcome is annualized relapse rate. Safety outcomes will include serious adverse events, meningococcal infections, and pregnancy, breastfeeding, and neonatal outcomes. Data will be collected prospectively for up to 5 years. Approximately 130 patients will be enrolled, with a maximum of around 200 patients in up to 10 countries globally. Results: N/A Conclusions: This registry will collect data to characterize the long-term effectiveness and safety of the C5ITs eculizumab and ravulizumab in patients with AQP4+ NMOSD to provide evidence on the real-world impact of C5ITs in this patient population.