As high visit-to-visit variability in cholesterol levels has been reported to be an independent predictor of major adverse cardiovascular events in patients with coronary artery disease, a study was conducted with an aim of determining the link between total cholesterol (TC) variability and the risk of all-cause mortality, myocardial infarction (MI), and stroke. A total of 3,656,648 individuals without a history of MI and stroke who underwent ≥ 3 health examinations from 2002 to 2007 were recruited. The results published in the Circulation journal showed that there were 84,625 deaths (2.3%), 40,991 cases of MI (1.1%), and 42,861 cases of stroke (1.2%) during the median follow-up of 8.3 years. A linear association was seen between higher TC variability and outcome measures. In the multivariable adjusted model, the hazard ratios and 95% confidence intervals that compared the highest versus lowest quartiles of coefficient of variation of TC were 1.26 (1.24–1.28) for all-cause mortality, 1.08 (1.05–1.11) for MI, and 1.11 (1.08–1.14) for stroke, and were independent of mean TC levels and the use of lipid-lowering agents. Thus, it was suggested that high variability in lipid levels is related to adverse health-related outcomes and appears to be an important risk factor in the general population.