National trends in age-standardised death rates (ASDRs) for non-communicable diseases (NCDs) in South Africa (SA) were identified between 1997 and 2010.As part of the second National Burden of Disease Study, vital registration data were used after validity checks, proportional redistribution of missing age, sex and population group, demographic adjustments for registration incompleteness, and identification of misclassified AIDS deaths. Garbage codes were redistributed proportionally to specified codes by age, sex and population group. ASDRs were calculated using mid-year population estimates and the World Health Organization world standard.Of 594 071 deaths in 2010, 38.9% were due to NCDs (42.6% females). ASDRs were 287/100 000 for cardiovascular diseases (CVDs), 114/100 000 for cancers (malignant neoplasms), 58/100 000 for chronic respiratory conditions and 52/100 000 for diabetes mellitus. An overall annual decrease of 0.4% was observed resulting from declines in stroke, ischaemic heart disease, oesophageal and lung cancer, asthma and chronic respiratory disease, while increases were observed for diabetes, renal disease, endocrine and nutritional disorders, and breast and prostate cancers. Stroke was the leading NCD cause of death, accounting for 17.5% of total NCD deaths. Compared with those for whites, NCD mortality rates for other population groups were higher at 1.3 for black Africans, 1.4 for Indians and 1.4 for coloureds, but varied by condition.NCDs contribute to premature mortality in SA, threatening socioeconomic development. While NCD mortality rates have decreased slightly, it is necessary to strengthen prevention and healthcare provision and monitor emerging trends in cause-specific mortality to inform these strategies if the target of 2% annual decline is to be achieved.