BACKGROUND: Human enteroviruses (EV) have been associated with severe acute respiratory illness (SARI) in South Africa. OBJECTIVES: We aimed to describe the molecular epidemiology of EV serotypes among patients hospitalized with SARI during 2009-2011. PATIENTS/METHODS: Study samples from patients were tested for the presence of enterovirus using a polymerase chain reaction assay. RESULTS: 8.2% (842/10 260) 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. CONCLUSIONS: EV-D68 should be monitored in South Africa to assess the emergence of highly pathogenic strains.