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Background The associations between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality are unclear in young adults (&amp;lt;45 years) and in Asian populations. Methods In total, 15 860 253 Korean adults underwent routine health examinations during 2009–10 and were followed until June 2018 for all-cause mortality. Hazard ratios (HRs) were calculated using Cox proportional hazard models. Results During a mean 8.4 years of follow-up, 555 802 individuals died. U-curve associations were found between HDL-C levels and mortality, irrespective of sex or age. The HDL-C ranges associated with the lowest mortality were 40–59 and 50–69 mg/dL (1.03–1.54 and 1.29–1.80 mmol/L) in men aged &amp;lt;65 and ≥65 years, respectively, and the corresponding ranges were 40–69 and 50–79 mg/dL (1.03–1.80 and 1.29–2.06 mmol/L) in women aged &amp;lt;45 and ≥45 years, respectively. For HDL-C ranges of 60–149 mg/dL (1.55–3.86 mmol/L), each 39 mg/dL (1 mmol/L) increase in HDL-C was associated with higher mortality [men: HR = 1.39; 95% confidence interval (CI) = 1.36–1.42; women: HR = 1.15, 95% CI = 1.11–1.18], adjusting for age. These positive associations were generally stronger at younger than older ages, whereas inverse associations for HDL-C ranges &amp;lt;60 mg/dL (1.55 mmol/L) were strongest in middle age (45–64 years). The U-curve associations were generally unchanged after adjustment for various confounders. Conclusions Korean adults showed U-curve associations of HDL-C with mortality, regardless of sex, and age. Younger adults had a lower optimal range and a stronger positive association with mortality than older adults in the high HDL-C range. Even moderately high HDL-C levels are not necessarily a sign of good health, especially in young adults.

High-density lipoprotein cholesterol and all-cause mortality by sex and age: a prospective cohort study among 15.8 million adults