Abstract: Objective To investigate the association between serum uric acid to high-density lipoprotein cholesterol ratio（UHR） and new-onset atherosclerotic cardiovascular disease（ASCVD）. Methods A prospective study was conducted in 95 418 employees of Kailuan Group who participated in standardized physical examination from 2006 to 2007.The study population was divided into four groups according to the UHR quartile: The first quartile（UHR＜142.17 μmol/mmol, n=23 859）, the second quartile（142.17-＜184.69 μmol/mmol, n=23 851）, the third quartile（184.69-＜240.46 μmol/mmol, n=23 857） and the fourth quartile（UHR≥240.46 μmol/mmol, n=23 851）.Kaplan-Meier method was used to calculate the cumulative incidence of new-onset ASCVD among each group, and Log-Rank was used to test the differences of cumulative incidence among the groups.Multivariate Cox regression model was used to analyze the effect of UHR on new-onset ASCVD. Results During a median follow-up of 14.94(P₂₅, P₇₅: 14.49-15.16) years, 11 517（12.1%） new-onset ASCVD cases were diagnosed.After adjusting for potential confounders, Cox proportional hazard models showed that compared with the subjects in the first quartile of UHR, the subjects in the third and fourth quartile had a 6.9%（HR=1.069, 95%CI 1.013-1.129） and 18.3%（HR=1.183, 95%CI 1.121-1.248） increased risk of ASCVD, respectively, the subjects in the fourth quartile had a 30.0%（HR=1.300, 95%CI 1.168-1.446） increased risk of heart failure, the subjects in the third and fourth quartile groups had a 12.4%（HR=1.124, 95%CI 1.022-1.236） and 27.1%（HR=1.271, 95%CI 1.157-1.396） increased risk of myocardial infarction and coronary revascularization, and the subjects in the fourth quartile had a 9.7%（HR=1.097, 95%CI 1.020-1.179） increased risk of ischemic stroke.The risk of ASCVD increased by 5%（HR=1.050, 95%CI 1.032-1.068） for every one standard deviation increase in UHR. There was interactions between UHR group and gender, age, hypersensitive C-reactive proteins（hsCRP）（all P＜0.05）.The results of stratification analysis by gender showed that compared with the first quartile, the HR（95%CI） value of ASCVD in the fourth quartile was 1.150（1.086-1.218） in the male population and 1.444（1.224-1.704） in the female population.The results of stratification analysis by age showed that compared with the first quartile, the HR（95%CI） values of ASCVD in the third and fourth quartile group were 1.091（1.012-1.177） and 1.228（1.138-1.325） respectively in the subjects aged 45-＜60 years old, the HR（95%CI） value of ASCVD in the fourth quartile group was 1.181（1.083-1.287） in the subjects aged ≥60 years old, but there was no significant difference in the subjects aged under 45 years old.The HR（95%CI） value was 1.112（1.041-1.187） in the population with hsCRP＜3 mg/L, while it was 1.346（1.224-1.479） in the population with hsCRP≥3 mg/L. Conclusions High UHR is a risk factor of ASCVD, and this relationship shows gender and age differences.The focus should be on women and middle-aged and elderly people（≥45 years old）. The effect of UHR on the risk of new-onset ASCVD may be more significant in the population with inflammatory disease（hsCRP≥3 mg/L）.Moreover, The risk of ASCVD may be organ-specific, with cardiovascular effects greater than cerebrovascular effects.