Background. Low-density lipoprotein cholesterol (LDL-C) is the most important contributor to atherosclerosis, a causal factor for ischaemic heart disease (IHD) and ischaemic stroke. Although raised LDL-C is a key contributor to cardiovascular disease (CVD), the exact attributable disease risk in South Africa (SA) is unknown. The the first SA comparative risk assessment (SACRA1) study assessed the attributable burden of raised total cholesterol, and not specifically LDL-C. Objectives. To estimate the national mean serum LDL-C by age, year and sex and to quantify the burden of disease attributable to LDL-C in SA for 2000, 2006 and 2012. Methods. The comparative risk assessment (CRA) method was used. Estimates of the national mean of LDL-C, representing the 3 different years, were derived from 14 small observational studies using a meta-regression model. A theoretical minimum risk exposure level (TMREL) of 0.7 - 1.3 mmol/L was used. LDL-C estimates together with the relative risks from the Global Burden of Disease Study 2017 were used to calculate a potential impact fraction (PIF). This was applied to IHD and ischaemic stroke estimates sourced from the Second National Burden of Disease Study. Attributable deaths, years of life lost, years lived with disability and disability-adjusted life years (DALYs) were calculated. Uncertainty analysis was performed using Monte Carlo simulation. Results. LDL-C declined from 2.74 mmol/L in 2000 to 2.58 mmol/L in 2012 for males, while in females it declined from 3.05 mmol/L in 2000 to 2.91 mmol/L in 2012. The PIFs for LDL-C showed a slight decline over time, owing to the slight decrease in LDL-C levels. Attributable DALYs increased between 2000 (n=286 712) and 2006 (n=315 125), but decreased thereafter in 2012 (n=270 829). Attributable age-standardised death rates declined between 2000 and 2012 in both sexes: in males from 98 per 100 000 members of the population in 2000 to 78 per 100 000 in 2012, and in females from 81 per 100 000 in 2000 to 58 per 100 000 in 2012. Conclusions. Mean LDL-C levels were close to 3 mmol/L, which is the recommended level at which cholesterol-lowering treatment should be initiated for people at low and moderate risk for cardiovascular outcomes. The decreasing trend in the age-standardised attributable burden due to LDL-C is encouraging, but it can be lowered further with the introduction of additional population-based CVD prevention strategies. This study highlights the fact that high LDL-C concentration in relation to the TMREL in SA is responsible for a large proportion of the emerging CVD, and should be targeted by health planners to reduce disease burden.