Abstract Background Multiple sclerosis (MS) is a leading cause of disability among young adults and effects considerable social and economic burdens. Data of MS incidence in China at the national level is lacking. We conducted the first nationwide hospital-based study to estimate the incidence and hospitalization burden of MS in China. Methods This study is based on an administrative database of the National Hospital Quality Monitoring System, which covers all 1665 tertiary hospitals in mainland China. The “Medical Record Homepage” of all patients, including 346 variables including demographic characteristics, diagnoses, procedures, and expenses etc., were uniformly collected across each tertiary hospital via standard protocol. MS was defined by the 2010 International Panel criteria for MS and was identified by ICD-10 code (G35•0). Findings We identified 27,336 hospital admissions for 15,060 MS patients from 2016 to 2018; amongst these patients, 9,879 were newly diagnosed. The age- and sex-adjusted incidence per 100,000 person-years is 0•235 (95% confidence interval [CI] 0•230–0•240), with 0•055 (0•050–0•060) in children and 0•288 (0•282–0•294) in adults, respectively. The female to male ratio is 2•02; the peak disease onset is age of 40–49 years. Residents in high-latitude and high-altitude areas are more likely to develop MS (F = 8•99; p Interpretation For the first time, we obtain the national incidence of MS as 0.055 in children and 0.288 in adults per 100,000 in China. The geographical distribution of MS incidence presented a north-south latitude gradient and a west-east altitude gradient. Funding National Science Foundation of China (81801199, 91642205, and 81830038); Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing.