Rare diseases require integrated multicenter clinical networks to facilitate clinical research. Neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSDs) are uncommon neuroinflammatory syndromes that are distinct from multiple sclerosis and associated with NMO-IgG, a serologic antibody against aquaporin 4. To develop a national multicenter NMO clinical consortium and report initial demographic, clinical, and radiographic features of a cohort of patients with NMO/NMOSD in the United States. Review of medical records from patients undergoing evaluation during a 5-year period. We used uniform diagnostic criteria and clinical, laboratory, and neuroimaging definitions to describe the cohort. Three academic medical centers. One hundred eighty-seven patients with NMO/NMOSD. Of the 187 patients included in the analysis, 86 had NMO-IgG-seropositive NMO; 40, NMO-IgG-seronegative NMO; and 61, NMO-IgG-seropositive NMOSD. Altogether, 29.4% of our patients were initially misdiagnosed with multiple sclerosis. The average age at onset of NMO/NMOSD was 41.1 years with a strong female predilection, similar to other autoimmune disorders. Nonwhite patients constituted 52.4% of the cohort. The hallmark of NMO and NMOSD is recurrent longitudinally extensive transverse myelitis, but patients with NMO tend to initially present with optic neuritis. A national multicenter consortium to study NMO/NMOSD is feasible and facilitates accurate clinical diagnosis. This network establishes a foundation for determining disease prevalence, translational research, and clinical trials.