Objective This study aimed to assess the effect of pregnancy on the course of neuromyelitis optica spectrum disorder (NMOSD), and the effect of this disease on pregnancy outcomes. Methods Consecutive patients with NMOSD were recruited between September 2015 and April 2016 at an outpatient clinic from four referral institutes in South China. Demographic, clinical, and pregnancy data were retrieved by questionnaires to analyze the association between NMOSD and pregnancy, as well as the potential risk factors for relapse. Results Among 249 patients with NMOSD, 55 had pregnancy-related attacks. The annual relapse rate in the first (3.20 ± 6.82) and second (3.25 ± 3.32) 3-month postpartum periods was marginally higher than that before pregnancy (1.44 ± 0.92, p = 0.682) and during pregnancy (1.23 ± 1.32, p = 0.758). The Kurtzke Expanded Disability Status Scale score increased from 1.55 ± 0.38 before pregnancy to 2.88 ± 2.14 at postpartum (p < 0.001). NMOSD significantly increased the premature birth rate in patients after disease onset (8.33%) compared with before disease onset (1.95%, p = 0.025). Multivariate analysis showed that negative anti-aquaporin-4 IgG, concomitance with autoimmune diseases/antibodies, and no treatment in remission were risk factors of recurrence. Conclusion Our study shows a significant association between pregnancy and NMOSD in the Chinese population. Larger scale prospective studies are warranted in the future.