Background.The contribution of human rhinovirus (HRV) to severe acute respiratory illness (ARI) is unclear.Objective.To assess the association between HRV species detection and ARI hospitalizations.Methods.Children <5 years old hospitalized for ARI were prospectively enrolled between December 2003 and April 2005 in 3 US counties. Asymptomatic controls were enrolled between December 2003 and March 2004 and between October 2004 and April 2005 in clinics. Nasal and throat swab samples were tested for HRV and other viruses (ie, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, and influenza virus) by reverse-transcription-polymerase chain reaction, and genetic sequencing identified HRV species and types. HRV species detection was compared between controls and patients hospitalized during months in which controls were enrolled.Results.A total of 1867 children with 1947 ARI hospitalizations and 784 controls with 790 clinic visits were enrolled and tested for HRV. The HRV-A detection rate among participants ≥24 months old was 8.1% in the hospitalized group and 2.2% in the control group (P =. 009), and the HRV-C detection rates among those ≥6 months old were 8.2% and 3.9%, respectively (P =. 002); among younger children, the detection rates for both species were similar between groups. The HRV-B detection rate was ≤1%. A broad diversity of HRV types was observed in both groups. Clinical presentations were similar among HRV species. Compared with children infected with other viruses, children with HRV detected were similar for severe hospital outcomes and more commonly had histories or diagnoses of asthma or wheezing.