Summary Background Data for trends in serum cholesterol are needed to understand the effects of its dietary, lifestyle, and pharmacological determinants; set intervention priorities; and evaluate national programmes. Previous analyses of trends in serum cholesterol were limited to a few countries, with no consistent and comparable global analysis. We estimated worldwide trends in population mean serum total cholesterol. Methods We estimated trends and their uncertainties in mean serum total cholesterol for adults 25 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (321 country-years and 3·0 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean total cholesterol by age, country, and year, accounting for whether a study was nationally representative. Findings In 2008, age-standardised mean total cholesterol worldwide was 4·64 mmol/L (95% uncertainty interval 4·51–4·76) for men and 4·76 mmol/L (4·62–4·91) for women. Globally, mean total cholesterol changed little between 1980 and 2008, falling by less than 0·1 mmol/L per decade in men and women. Total cholesterol fell in the high-income region consisting of Australasia, North America, and western Europe, and in central and eastern Europe; the regional declines were about 0·2 mmol/L per decade for both sexes, with posterior probabilities of these being true declines 0·99 or greater. Mean total cholesterol increased in east and southeast Asia and Pacific by 0·08 mmol/L per decade (−0·06 to 0·22, posterior probability=0·86) in men and 0·09 mmol/L per decade (−0·07 to 0·26, posterior probability=0·86) in women. Despite converging trends, serum total cholesterol in 2008 was highest in the high-income region consisting of Australasia, North America, and western Europe; the regional mean was 5·24 mmol/L (5·08–5·39) for men and 5·23 mmol/L (5·03–5·43) for women. It was lowest in sub-Saharan Africa at 4·08 mmol/L (3·82–4·34) for men and 4·27 mmol/L (3·99–4·56) for women. Interpretation Nutritional policies and pharmacological interventions should be used to accelerate improvements in total cholesterol in regions with decline and to curb or prevent the rise in Asian populations and elsewhere. Population-based surveillance of cholesterol needs to be improved in low-income and middle-income countries. Funding Bill & Melinda Gates Foundation and WHO.