Background. Physical activity is associated with a lower risk of cardiovascular outcomes, certain cancers and diabetes. The previous South African Comparative Risk Assessment (SACRA1) study assessed the attributable burden of low physical activity for 2000, but updated estimates are required, as well as an assessment of trends over time.Objective. To estimate the national prevalence of physical activity by age, year and sex and to quantify the burden of disease attributable to low physical activity in South Africa (SA) for 2000, 2006 and 2012.Methods. Comparative risk assessment methodology was used. Physical activity was treated as a categorical variable with four categories, i.e. inactive, active, very active and highly active. Prevalence estimates of physical activity levels, representing the three different years, were derived from two national surveys. Physical activity estimates together with the relative risks from the Global Burden of Disease, Injuries, and Risk Factors (GBD) 2016 study were used to calculate population attributable fractions due to inactive, active and very active levels of physical activity relative to highly active levels considered to be the theoretical minimum risk exposure (>8 000 metabolic equivalent of time (MET)-min/wk), in accordance with the GBD 2016 study. These were applied to relevant disease outcomes sourced from the Second National Burden of Disease Study to calculate attributable deaths, years of life lost, years lived with disability and disability adjusted life years (DALYs). Uncertainty analysis was performed using Monte Carlo simulation.Results. The prevalence of physical inactivity (<600 METS) decreased by 16% and 8% between 2000 and 2012 for females and males, respectively. Attributable DALYs due to low physical activity increased between 2000 (n=194 284) and 2006 (n=238 475), but decreased thereafter in 2012 (n=219 851). The attributable death age-standardised rates (ASRs) declined between 2000 and 2012 from 60/100 000 population in 2000 to 54/100 000 population in 2012. Diabetes mellitus type 2 displaced ischaemic heart disease as the largest contributor to attributable deaths, increasing from 31% in 2000 to 42% in 2012.Conclusions. Low physical activity is responsible for a large portion of disease burden in SA. While the decreased attributable death ASR due to low physical activity is encouraging, this burden may be lowered further with an additional reduction in the overall prevalence of physical inactivity, in particular. It is concerning that the attributable burden for diabetes mellitus is growing, which suggests that existing non-communicable disease policies need better implementation, with ongoing surveillance of physical activity, and population- and community-based interventions are required in order to reach set targets.