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Objective:Inconsistencies exist regarding the relationships between prolactin (PRL), Chronic Kidney Disease (CKD), and Cardiovascular Diseases (CVD). In the present population-based study with an average of 20 years of follow-up, we aimed to investigate the impact of PRL levels on CVD events and its interaction with CKD in both sexes. Material and methods: The present study included a total of 2,005 participants of the Tehran Lipid and Glucose Study (TLGS) who met the inclusion criteria. They were re-assessed (approximately every three years for a median follow-up of 19.0 years. (Interquartile range (IQR):16.4 – 20.2), during which occurrences of chronic kidney disease (CKD) and cardiovascular disease (CVD) events were recorded. A pooled logistic regression model was employed to examine the influence of Prolactin on CVD events, as well as its interaction with CKD. Results: During follow-up, 156 and 73 incident CVD have occurred in men and women, respectively. Median (95%CI) for PRL was 7.4(5.5-10.5) ng/mL for men and 15.2(10.3-23) ng/mL for women. Increased prolactin had no statistically significant effect on odds of CVD in unadjusted and adjusted models, for men and women. The odds of CVD in men with a history of CKD was 3.41 (95% CI: 1.91–6.10; PConclusion: the effect of CKD on CVD risk is not significantly influenced by the level of prolactin. Further research is necessary to fully comprehend the relationship between prolactin, chronic kidney disease, and cardiovascular disease.