Background Human adenoviral infections typically result in upper respiratory tract infections, conjunctivitis, and gastroenteritis that is classically self-limiting but can be life-threatening in immunocompromised individuals. In relatively rare cases, adenovirus infections in immunocompetent patients can result in hospitalizations and severe outcomes that include need for critical care or death. The risk factors that are associated with severe adenoviral infections in immunocompetent hosts have not been thoroughly investigated and are currently poorly understood. Methods Retrospective cohort of 78 patients with ages ranging from 18–85 years who were admitted to Yale New Haven-affiliated hospitals over a period of 2 years with positive adenovirus tests on a nasopharyngeal respiratory viral panel. Immunocompromised patients were excluded from the study. Patient charts were reviewed to obtain demographic information, comorbid conditions, smoking history, and clinical outcomes. Results Of the 78 patients admitted, 15 (19.2%) were admitted as observation, 44 (56.4%) were admitted to the hospital for over 48 hours, 15 (19.2%) required critical care, and 4 (5.1%) expired during hospitalization. Pulmonary disease as a comorbidity in the form of asthma (33.3%) or chronic obstructive pulmonary disease (12.8%), and smoking history (59.0%) were more common in those with severe adenoviral infections. With severe disease, 13 (16.7%) required mechanical ventilation, 10 (12.8%) required pressor support, and 2 (2.6%) required extracorporeal membrane oxygenation. Conclusions This retrospective study characterizes severity of adenoviral infections in adult immunocompetent patients, highlights the lack of treatment available, and identifies potential risk factors for severe disease, including asthma, smoking, absence of fever, and presence of coinfection.