Heat waves are, amongst other weather hazards, projected to increase in frequency and intensity due to climate change. This increase has already been evident in parts of South Africa in the recent years. Their negative impacts are felt in many areas, including human health. This study aims to identify the most appropriate meteorological index for forecasting heat waves over South Africa and use it to develop an operational, numerical weather forecast based prediction system that will issue alerts whenever heat waves are expected. Data from temperature and relative humidity subsets from National Centers for Environmental Prediction (NCEP) Ensemble Forecast System (EFS), and observational temperature and dew-point temperature data from the South African Weather Service are used to evaluate and identify the most appropriate meteorological heat index, and to evaluate the model’s skill in heat wave forecasting. A number of evaluation matrices, including bias, symmetric external dependence index and Clayton skill scores, are used for evaluation. Recent heat wave events are also used to identify the synoptic patterns that cause heat waves. This is achieved by plotting the mean sea-level pressure heights and 850hPa and 500hPa geopotential heights from NCEP reanalysis data for these cases. Since there is no evidence that the impacts of heat waves on human health have to date been conducted in South Africa, this study uses international literature to identify the best practices that can be used to prevent or mitigate the negative impacts of heat waves on human health. The Humidex index is identified as the most suitable index for forecasting heat waves over South Africa and has benefit in the skill of up to five days ahead. This implies that heat wave warnings can be issued with confidence 1-5 days ahead of the phenomenon. Eight heat wave cases were identified between 2011 and 2015, and most of them occurred over the eastern interior of the country. These heat waves are caused by the presence of a broad surface trough over the interior that extends from the tropics, with no moisture influx from the Indian Ocean (IO), along with an upper-air high-pressure system over the central interior. Heat waves over the east coast are caused by the presence of a ridging high or continental high that are located in such a way that the east coast is on an off-shore flow. A ridging high that would normally cause berg winds and veld fires over the Western Cape is also the cause of heat waves. The heat-health watch-warning systems in other parts of the world are effective due to the involvement of different stakeholders. The same approach is recommended for adoption over South Africa. With the involvement of different sectors, and with the health sector taking the lead, the system is expected to accomplish the desired outcome.