BACKGROUND: Acute respiratory infection (ARI) poses a significant public health challenge worldwide, particularly among older adults. However, the disease and economic burden of ARI among older adults in China remained sparse. We aimed to estimate the incidence rate and medical cost of hospitalisation due to ARI among adults aged ≥50 years in Jiangsu Province, China. METHODS: We analysed medical records of hospitalised episodes due to ARI from January 2019 to May 2023 from a regionally representative medical database. We estimated hospitalisation rates and the proportion of severe cases (intensive care unit admission, mechanical ventilation, or death) by sex, age group, and time period. Total direct medical cost and out-of-pocket cost were estimated in CNY. We analysed factors influencing total costs using a multivariate linear regression model. We further compared the proportion of severe cases and medical cost between those with and without selected comorbidities. RESULTS: A total of 209 632 episodes of ARI hospitalisation were included. Over the study period, annualised ARI hospitalisation rate ranged from 1.07 to 1.83 per 1000 person-years, and varied by age, sex and region. Severe cases accounted for 6.5-10.3%. The median total direct medical cost was CNY 9027 (interquartile range (IQR) = 6118-14 886), of which 22% (IQR = 7-41) was out-of-pocket. Rural residents born a substantial out-of-pocket cost, which was even higher than their average monthly disposable income. Patients with certain comorbidities had higher medical costs despite having a similar or even lower proportion of severe cases. CONCLUSIONS: By analysing a large regionally representative medical database, we helped address the knowledge gap in the burden and cost of ARI hospitalisation in China. While highlighting the overall substantial disease burden and cost of ARI, we identified important factors such as age, sex, region, and comorbidity that influence the disease burden and cost of ARI.