Objective <p>This study aims to explore the associations between birth interval and prevalence of chronic kidney disease (CKD) in United States (U.S.) postmenopausal women with two deliveries.</p> Methods <p>The study utilized data from the National Health and Nutrition Examination Survey (NHANES) covering 1999 to 2018, which is publicly available. Weighted multivariable logistic regression, subgroup analysis and restricted cubic spline (RCS) models were used to study association of reproductive factors (birth interval) with CKD risk in postmenopausal women with two deliveries. Additionally, the association of age at first birth (AFB) and age at last birth (ALB) with CKD risk have also been explored by the above-mentioned methods.</p> Results <p>A total of 2953 postmenopausal women with two deliveries only were included in the study, and 271 (11.4%) had CKD. RCS models showed that AFB, ALB and birth interval all were U-shape curve associated with CKD risk in postmenopausal women with two deliveries. After adjusting for confounding factors, compared with the lowest quartiles, the odds ratios with 95% confidence intervals for CKD across the quartiles were ((0.73 (0.44, 1.21), 0.68 (0.39, 1.20), and 1.28 (0.94, 2.07)), (0.49 (0.31, 0.77), 0.60 (0.36, 0.98), and 0.61 (0.34, 1.12)) and (0.91 (0.54, 1.56), 0.84 (0.52, 1.34), and 1.05 (0.64, 1.72)) for AFB, ALB and birth interval.</p> Conclusions <p>AFB, ALB and birth interval demonstrated U-shaped relationships with CKD risk among postmenopausal women with two deliveries. These results highlight the association between reproductive history and long-term kidney health, and could inform CKD prevention strategies for U.S. postmenopausal women.</p> Clinical trial number <p>Not applicable.</p>