This study investigated the association between low-density lipoprotein cholesterol (LDL-C) levels and mortality in populations with different atherosclerotic cardiovascular disease (ASCVD) risk profiles in China. A total of 3,789,025 participants aged 35-75 years from 31 provinces in mainland China were included in the analysis. The participants were categorized into low-risk, primary prevention, and secondary prevention cohorts based on their medical history and ASCVD risk. The median LDL-C concentration was 93.1 mg/dL at baseline, and over a median follow-up of 4.6 years, 92,888 deaths were recorded, including 38,627 cardiovascular deaths. The association between LDL-C levels and mortality was U-shaped in the low-risk and primary prevention cohorts, and J-shaped in the secondary prevention cohort. The LDL-C levels corresponding to the lowest cardiovascular disease (CVD) mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. The LDL-C levels associated with the lowest all-cause mortality were 90.9 mg/dL and 117.0 mg/dL, and for CVD mortality, 87 mg/dL and 114.6 mg/dL. These levels were lower in individuals with diabetes than in those without diabetes. The study found that the association between LDL-C and mortality varied among different ASCVD risk cohorts, suggesting that stricter lipid control targets may be needed for individuals with higher ASCVD risk and those with diabetes. The findings indicate that lipid management strategies should be differentially performed in individuals at different ASCVD risk levels. The study also highlights the importance of lipid management for primordial prevention, where individuals with a low risk of ASCVD but high LDL-C levels should receive lipid-lowering medications or health behavior education. The study concludes that higher LDL-C levels are associated with increased all-cause and CVD mortality in populations with stratified ASCVD risks.This study investigated the association between low-density lipoprotein cholesterol (LDL-C) levels and mortality in populations with different atherosclerotic cardiovascular disease (ASCVD) risk profiles in China. A total of 3,789,025 participants aged 35-75 years from 31 provinces in mainland China were included in the analysis. The participants were categorized into low-risk, primary prevention, and secondary prevention cohorts based on their medical history and ASCVD risk. The median LDL-C concentration was 93.1 mg/dL at baseline, and over a median follow-up of 4.6 years, 92,888 deaths were recorded, including 38,627 cardiovascular deaths. The association between LDL-C levels and mortality was U-shaped in the low-risk and primary prevention cohorts, and J-shaped in the secondary prevention cohort. The LDL-C levels corresponding to the lowest cardiovascular disease (CVD) mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. The LDL-C levels associated with the lowest all-cause mortality were 90.9 mg/dL and 117.0 mg/dL, and for CVD mortality, 87 mg/dL and 114.6 mg/dL. These levels were lower in individuals with diabetes than in those without diabetes. The study found that the association between LDL-C and mortality varied among different ASCVD risk cohorts, suggesting that stricter lipid control targets may be needed for individuals with higher ASCVD risk and those with diabetes. The findings indicate that lipid management strategies should be differentially performed in individuals at different ASCVD risk levels. The study also highlights the importance of lipid management for primordial prevention, where individuals with a low risk of ASCVD but high LDL-C levels should receive lipid-lowering medications or health behavior education. The study concludes that higher LDL-C levels are associated with increased all-cause and CVD mortality in populations with stratified ASCVD risks.