Background and Aim: Asthma is the most common chronic illness in South African children and its prevalence is increasing in both urban and rural areas. Little is known about the prevalence of asthma amongst pre-school children living in Mpumalanga province, South Africa, which forms part of the Highveld region, a priority area in terms of air pollution. The area is known for poor air quality and elevated concentrations of criteria pollutants. The aim of the study was to investigate the prevalence of asthma and asthma symptoms among rural and urban pre-school children and the association with environmental risk factors. Methods: This analytical cross-sectional study that included 3145 pre-school children from Mpumalanga Province, South Africa. Parents of the children were requested to complete a modified ISAAC questionnaire. We analyzed the influence of potential risk factors on dependent variables using bivariate analysis. Significant risk factors identified in the bivariate analysis were included in a multiple logistic regression to develop a final model. Results: Self-reported prevalence of asthma was 2.3% (66/2810), with pre-school children in rural areas reporting a higher rate than pre-school children in urban areas (1.3% vs 1%), χ2=10.86, P <0.001). The prevalence of asthma symptoms was 15.1% (467/3084), with rural pre-school children reporting a higher prevalence of symptoms than urban pre-school children (10% vs 5%), χ2 = 24.45, P < 0.001). Risk factors for asthma and asthma symptoms were vigorous physical activity (odds ratio (OR) 2.31, 95% CI 1.14-4.66), home smoking exposure (OR 2.94, 95% CI 1.40-6.19) and male parent smoking (OR 1.46, 95% CI 1.01-2.12). Conclusions: Pre-school children in rural areas reported a higher prevalence of asthma compared to pre-school children in urban areas. Risk factors for asthma included physical activity and smoking exposure in the home. Key words: asthma, pre-school children, risk factors