Using the GeoSentinel database, an analysis of ill patients returning from throughout sub-Saharan Africa over a 13-year period was performed. Systemic febrile illness, dermatologic, and acute diarrheal illness were the most common syndromic groupings, whereas spotted fever group rickettsiosis was the most common individual diagnosis for travelers to South Africa. In contrast to the rest of sub-Saharan Africa, only six cases of malaria were documented in South Africa travelers. Vaccine-preventable diseases, typhoid, hepatitis A, and potential rabies exposures were uncommon in South Africa travelers. Pre-travel advice for the travelers to the 2010 World Cup should be individualized according to these findings.