OBJECTIVE: To investigate the mixed infection and analyze risk factors in children with severe adenovirus pneumonia. METHODS: A retrospective analysis was performed on the clinical data of 756 children with adenovirus pneumonia between June 2009 and June 2011. Pathogens and risk factors were studied in 216 severe cases. RESULTS: Of the 216 severe cases, 138 (63.9%) were aged from 6 months to 2 years, and 161 (74.5%) developed the disease in the winter and spring; 177 (81.9%) were affected by 1-4 pathogens besides adenovirus, including 74 cases (34.3%) infected with one pathogen as an addition. A total of 334 pathogen strains were identified from the respiratory secretions and sera of the 216 cases. Of them, 163 (48.8%) were bacterial strains, dominated by Gram-negative bacteria (124 strains), 108 (32.3%) were viral strains, and 40 (12.0%) were fungal strains. Multivariate logistic regression analysis indicated that congenital heart disease, congenital airway abnormalities, nutritional anemia, recurrent pulmonary infection, and surgical history were the independent risk factors for severe adenovirus pneumonia in children, with odds ratios of 3.3, 11.1, 7.2, 14.3 and 12.9 respectively (P<0.05). CONCLUSIONS: Severe adenovirus pneumonia is mostly seen in children aged from 6 months to 2 years and occurs frequently in the winter and spring. Many cases are also infected with other pathogens, most commonly Gram-negative bacteria. Congenital heart disease, congenital airway abnormalities, nutritional anemia, recurrent pulmonary infection and surgical history are the independent risk factors for severe adenovirus pneumonia in children.