To evaluate epidemiology and risk factors of severe adenovirus respiratory infection in hospitalized children in Guangzhou, China.A retrospective review study was conducted, and 542 children hospitalized for adenovirus respiratory infection, were included from January 2011 to December 2014. Patients were younger than 14 years. Disease severity was classified into severe and mild. Laboratory tests and clinical characteristics were analyzed for risk factors of adenovirus respiratory infection by multivariable logistic regression.Among these 542 children, 92.1% were aged < 6 years. Clinical diagnoses were upper respiratory infections in 11.6%, bronchiolitis in 16%, and mild pneumonia in 62.0% of children. Severe pneumonia rate was 10.3% (56/542) with a mortality rate of 0.9% (5/542). The cohort comprised 542 patients; 486 patients with mild adenovirus respiratory infection and 56 patients with severe adenovirus respiratory infection. Multivariable logistic regression was used to confirm associations between variables and adenovirus respiratory infection, after age and gender adjustment. Hospital stay, still significantly associated with adenovirus respiratory infection. Patients with longer hospital stay (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.13-1.28, P < .001), lower LYMPH (OR = 0.73 95% CI: 0.55-0.99, P = .039), and increased LDH (OR = 1.002, 95% CI: 1.001-1.003, P = .001) had a higher risk of severe adenovirus respiratory infection.Adenovirus is a major pathogen in hospitalized children with respiratory infection. High serum LDH level and low lymphocyte count could be used as predictors of adenovirus respiratory infection severity in children.