Objective: Cross-sectional study of the association between serum High-density lipoprotein cholesterol (HDL-C) and Reproductive lifespan (RLS) in postmenopausal women in the United States. Methods：Analyzed 752 postmenopausal female participants from the 2021-2023 National Health and Nutrition Examination Survey (NHANES) database. The correlation between HDL-C and RLS was investigated using multiple linear regression models, and the stability of the relationship between HDL-C and RLS was assessed using subgroup analyses and interaction tests. Results: After adjusting for various confounders, we found a significant positive association between HDL-C and RLS. The HDL-C-RLS relationship remained positive in most subgroups, with interaction tests showing that this relationship was not associated with any stratified subgroups. Conclusions: We found that higher HDL-C was significantly associated with increased RLS and that HDL-C has potential as a biomarker for early prediction of reproductive longevity in women.