Purpose: Stroke patients have a high incidence of comorbidity. Our study aimed to explore the trend of comorbidity among patients with first stroke from 2010 to 2020, and the influence of comorbidity on admission mortality, length of stay and hospitalization costs.5988 eligible patients were enrolled in our study, and divided into 4 comorbidity burden groups according to Charlson comorbidity index (CCI): none, moderate, severe, very severe. Survival analysis was expressed by Kaplan - Meier curve. Cox regression model was used to analyze the effect of comorbidity on 7-day and in-hospital mortality. Generalized linear model (GLM) was used to analyze the association between comorbidity and hospitalization days and cost. Results: Compared to patients without comorbidity, those with very severe comorbidity were more likely to be male (342, 57.7%), suffer from ischemic stroke (565, 95.3%), afford higher expense (Midian, 19339.3RMB, IQR13020.7-27485.9RMB), and have a higher in-hospital mortality (60, 10.1%). From 2010 to 2020, proportion of patients with severe and very severe comorbidity increased 12.9%. The heaviest comorbidity burden increased the risk of 7-day mortality (adjusted hazard ratio, 3.51, 95% CI, 2.22-5.53) and in-hospital mortality (adjusted hazard ratio, 3.83, 95% CI, 2.70-5.45). Patients with very severe comorbidity had a 12% longer LOS and extra 27% expense than those without comorbidity.Conclusion: Comorbidity burden showed an increasing trend year in past eleven years. The heavy comorbidity burden increased in-hospital mortality, LOS, and hospitalization cost, especially in patients aged 55 years or more.