Neuromyelitis optica spectrum disorder (NMOSD) has unknown risk factors. The aim of this study was to identify the environmental risk factors for NMOSD. A case–control study was conducted in Tehran from 2015 to 2016 among 100 patients with NMOSD. Sex-matched healthy controls (n = 400) were selected through random digit dialing (RDD). Logistic regression was used to estimate unadjusted and adjusted ORs (odds ratio) at 95% confidence intervals (CI) via SPSS. Compared with the control population, in NMOSD patients, the adjusted OR for low dairy consumption per week was (OR = 18.09; 95% CI 6.91, 47.37), following low sea food intake (OR = 13.91; 95% CI 6.13, 31.57) and low fruit and vegetable consumption (OR = 6.23; 95% CI 3.07, 12.62). The lower heavy physical activity (OR: 16.11, 95% CI 7.03, 36.91) among patients had risen the risk of NMOSD. A past history of head trauma was considered a risk for NMOSD (OR: 8.39, 95% CI 4.97, 14.16). The association between NMOSD and intentional abortion only among females (OR: 7.42, 95% CI 2.81, 19.55) was detected. This study indicates significant associations between dietary habits, life style, history of head trauma and intentional abortion in female and the later diagnosis of NMOSD.