AbstractBackgroundStudies have found that the ratio of total cholesterol to high‐density lipoprotein cholesterol (TC/HDL‐C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females.MethodsBased on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL‐C, TC/HDL‐C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve.ResultsDuring a mean follow‐up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL‐C and TC/HDL‐C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05–1.31), 0.84 (0.71–0.99), and 1.15 (1.06–1.25) for males, 0.94 (0.78–1.13), 0.58 (0.35–0.95), and 1.19 (1.01–1.40) for females, respectively. The results also showed that TC, HDL‐C, and TC/HDL‐C were associated with CKD in a linear dose–response relationship. The TC/HDL‐C had the largest area under the curve (AUC) compared to TC and HDL‐C, and the AUC among the females was larger than that among males.ConclusionsThe TC/HDL‐C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL‐C, especially in females.