Background: There have been no reports regarding the natural course of CSU using a population-based database. Objectives: The purpose of our study was to investigate natural course and comorbidities and of CSU using the Korean National Health Insurance Service National Sample Cohort 2002-2013. Methods: We enrolled patients into a CSU group (N=4,281) and an age- and sex-matched control group (N=21,405) between 2003 and 2007. Demographic data and comorbidities were compared between cases and controls. CSU remission rates were calculated in 1, 2, 3, 4, and 5 years after initial diagnosis. Demographic differences and profiles of comorbidities were analyzed between patients who underwent CSU remission within 1 year and patients who did not. Results: Proportions of metabolic, autoimmune, chronic infectious, allergic, and H. pylori-related diseases in the CSU group were significantly higher, compared to the control group. CSU remission rates 1, 2, 3, 4, and 5 years after initial diagnosis were 30.74%, 42.44%, 47.21%, 49.12%, and 50.29%, respectively. Age greater than 65 years, male sex, a history of type 2 diabetes mellitus, hypertension, and dyslipidemia were poor prognostic factors affecting the 1-year remission rate. In contrast, age younger than 19 years, Grave’s disease, and asthma were good prognostic factors. Conclusion: Results from this study will help to highlight both awareness of comorbidities and chronicity of CSU.