We evaluated the association between annual malaria incidence and El Niño Southern Oscillation (ENSO) as measured by the Southern Oscillation Index (SOI) in five countries in Southern Africa from 1988 to 1999. Below normal incidence of malaria synchronised with a negative SOI (El Niño) and above normal incidence with a positive SOI (La Niña), which lead to dry and wet weather conditions, respectively. In most countries there was a positive relationship between SOI and annual malaria incidence, especially where Anopheles arabiensis is a major vector. This mosquito breeds in temporary rain pools and is highly sensitive to fluctuations in weather conditions. South Africa and Swaziland have the most reliable data and showed the strongest associations, but the picture there may also be compounded by the moderating effect of other oscillatory systems in the Indian Ocean. The impact of ENSO also varies over time within countries, depending on existing malaria control efforts and response capacity. There remains a need for quantitative studies that at the same time consider both ENSO-driven climate anomalies and non-ENSO factors influencing epidemic risk potential to assess their relative importance in order to provide an empirical basis for malaria epidemic forecasting models.