ABSTRACT: BACKGROUND:Previous studies have revealed that triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) is one of major risk factors of insulin resistance and diabetes. However, study on the association between TG/HDL-C and diabetes mellitus (DM) risk is limited, especially in Chinese people. This study was undertaken to investigate the relationship between TG/HDL-C and incident of diabetes in a large cohort in Chinese population. METHODS:The present study was a retrospective cohort study. A total of 114,787 adults from Rich Healthcare Group in China, which includes all medical records for participants who received a health check from 2010 to 2016. The target independent variable and the dependent variable were triglyceride to high-density lipoprotein cholesterol ratio measured at baseline and incident of diabetes mellitus appeared during follow-up respectively. Covariates involved in this study included age, gender, body mass index, diastolic blood pressure, systolic blood pressure, fasting plasma glucose, total cholesterol, low density lipoprotein cholesterol, serum creatinine, smoking and drinking status and family history of diabetes. Cox proportional-hazards regression was used to investigate the association of TG/HDL-C and diabetes. Generalized additive models was used to identify non-linear relationships. Additionally, we also performed a subgroup analysis. It was stated that the data had been uploaded to the DATADRYAD website. RESULT:After adjusting age, gender, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low density lipoprotein cholesterol, serum creatinine, smoking and drinking status and family history of diabetes, result showed TG/HDL-C was positively associated with incident of diabetes mellitus (HR?=?1.159, 95%CI (1.104, 1.215)). A non-linear relationship was detected between TG/HDL-C and incident of diabetes, which had an inflection point of TG/HDL-C was 1.186. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.718(1.433,2.060) and 1.049(0.981,1.120), respectively. Subgroup analysis showed, the stronger association can be found in the population with fasting plasma glucose (FPG)