Adenovirus serotype 14 (Ad14) is a rarely reported but emerging serotype of adenovirus that can cause severe and sometimes fatal respiratory illness in patients of all ages, including healthy young adults. In May 2006, an infant in New York aged 12 days died from respiratory illness caused by Ad14. During March-June 2007, a total of 140 additional cases of confirmed Ad14 respiratory illness were identified in clusters of patients in Oregon, Washington, and Texas. Fifty-three (38%) of these patients were hospitalized, including 24 (17%) who were admitted to intensive care units (ICUs); nine (5%) patients died. Ad14 isolates from all four states were identical by sequence data from the full hexon and fiber genes. However, the isolates were distinct from the Ad14 reference strain from 1955, suggesting the emergence and spread of a new Ad14 variant in the United States. No epidemiologic evidence of direct transmission linking the New York case or any of the clusters was identified. This report summarizes the investigation of these Ad14 cases by state and city health authorities, the U.S. Air Force, and CDC. State and local public health departments should be alert to the possibility of outbreaks caused by Ad14.