Summary Objectives It is well established that respiratory viruses are an important cause of hospitalizations in young children worldwide, but data are limited on the contribution of specific viruses to severe illness in South America. We describe clinical and laboratory findings from prospective surveillance for acute respiratory infections at a tertiary hospital in São Paulo, Brazil. Methods We screened children < 2 years old with acute respiratory tract infections admitted to an urban tertiary hospital for respiratory viruses from March 2008 through February 2010, using polymerase chain reaction assays. Results Respiratory viruses were identified in 378 (53%) of the 715 samples analyzed. Respiratory syncytial virus was the most commonly identified virus (52%), followed by adenovirus (27%) and Human metapneumovirus (12%). More than one virus was identified in 19% of specimens. Almost half of the samples (46%) were from children with underlying health conditions. We demonstrated that compared to the previously healthy group, those with comorbidities had a worse outcome in terms of severity, with prolonged hospital stay and more need of intensive care. Conclusion Identification of this high-risk population along with strategies for fast diagnosis might each help to reduce morbidity and mortality in this group.