BACKGROUND: Lowering elevated low-density lipoprotein cholesterol (LDL-C) levels is a key strategy in primary prevention of atherosclerotic cardiovascular disease (ASCVD), but the optimal LDL-C level is not well established in Chinese. OBJECTIVE: We aimed to search for the LDL-C level that associated with the lowest long-term ASCVD risk without excess risk of other life-threatening diseases. METHODS: Totally 20,954 participants aged 35-64 years were followed up for about 20 years. Cumulative and relative risks of ASCVD, hemorrhagic stroke, and cancer death, according to baseline LDL-C levels, were calculated using modified Kaplan-Meier and Fine & Gray models, considering competing risks. Preventable ASCVD cases against increased harms were estimated by simulation, replacing elevated LDL-C levels with lower LDL-C levels in the risk prediction models for individuals with different ASCVD risk. RESULTS: The lower the baseline LDL-C, the lower the 20-year risk of ASCVD in participants with LDL-C levels ranging from the lowest category (<40 mg/dL) to the highest (>= 160 mg/dL). We found no association between lower LDL-C levels and long-term risk of cancer death. If all people with LDL-C >= 130 mg/dL were assumed to have the LDL-C level <70 mg/dL and other risk factors remained unchanged, a substantial number of ASCVD cases would be preventable. However, for uncontrolled hypertensive patients, the LDL-C level <70 mg/dL would have extra harm from hemorrhagic stroke. CONCLUSION: Participants with baseline LDL-C <40 mg/dL had the lowest ASCVD risk. An excess risk of hemorrhagic stroke was observed in patients with uncontrolled hypertension and LDL-C <70 mg/dL. LDL-C 70-99 mg/dL had reasonably low ASCVD risk without excess risk of other life-threatening diseases. (C) 2018 National Lipid Association. All rights reserved.