BackgroundHuman enteroviruses (EV) have been associated with severe acute respiratory illness (SARI) in South Africa. ObjectivesWe aimed to describe the molecular epidemiology of EV serotypes among patients hospitalized with SARI during 2009-2011. Patients/MethodsStudy samples from patients were tested for the presence of enterovirus using a polymerase chain reaction assay. Results8.2% (842/10260) of SARI cases tested positive for enterovirus; 16% (7/45) were species EV-A, 44% (20/45) EV-B, 18% (8/45) EV-C and 22% (10/45) EV-D. Seventeen different EV serotypes were identified within EV-A to EV-D, of which EV-D68 (22%; 10/45) and Echovirus 3 (11%; 5/45) were the most prevalent. ConclusionsEV-D68 should be monitored in South Africa to assess the emergence of highly pathogenic strains.