Objective To study the clinical features of Mycoplasma pneumoniae pneumonia (MPP) with adenovirus (ADV) infection in children. Methods A retrospective analysis was performed on the medical data of 228 children with MPP alone and 28 children with MPP and ADV infection. The two groups were compared in terms of clinical features, laboratory results, and treatment outcome. Results Compared with the MPP group, the MPP+ADV group had significantly longer duration of fever and length of hospital stay, a significantly higher proportion of patients with severe lesions (erosion and exfoliation) of the airway mucosa under bronchoscopy, a significantly higher clinical pulmonary infection score, and a significantly higher proportion of patients requiring oxygen therapy (P<0.05). There were no significant differences between the two groups in white blood cell count, C-reactive protein, Mycoplasma pneumoniae DNA copy number in bronchoalveolar lavage fluid, and the incidence rates of pleural effusion and extrapulmonary complications (P>0.05). Conclusion Compared with children with MPP alone, children with MPP and ADV infection tend to have more severe clinical manifestations and airway mucosal lesions and are more likely to require oxygen therapy, but most of the laboratory markers lack specificity.