There is debate whether atypical enteropathogenic E. coli (aEPEC) causes disease in adults. aEPEC is commonly detected in symptomatic and asymptomatic individuals. aEPEC, in contrast to typical EPEC, lacks bundle forming pili, altering its pathogenicity. Here we define for the first time the clinical manifestations of sporadic aEPEC infection in US children and adults and determine if EPEC load correlates with disease.