Both the clearance and secretion of prolactin are disrupted in chronic kidney disease (CKD). Evidence indicates that prolactin may play a role in cardiovascular (CV) disturbances. Considering the increased cardiovascular risk associated with CKD, this study investigates the relationship between prolactin levels, CKD, and the risk of CV events in both women and men, with an average follow-up period of 20 years. The study included 2,005 participants from the Tehran Lipid and Glucose Study (TLGS) who met the inclusion criteria. They were reassessed approximately every three years for a median follow-up of 19.0 years (Interquartile range (IQR):16.4-20.2), during which occurrences of CKD and CV events were recorded. A pooled logistic regression model examined the influence of Prolactin on CV events and its interaction with CKD. During follow-up, we identified 156 incident cases of CV events among men and 73 among women. Median (95%CI) PRL levels were 7.4 (5.5-10.5) ng/mL for men and 15.2 (10.3-23) ng/mL for women. The results of analyses showed that a history of CKD was associated with significantly higher odds of CV events for both men 4.2 (95% CI: 2.6-6.8) and women 5.5 (95% CI: 2.6-11.5). Results remained unchanged after adjustment for confounders including age, waist circumference, smoking, education, history of diabetes and hypertension, and family history of CV events. Interaction analyses revealed no statistically significant interaction between CKD and PRL on the odds of CV events in unadjusted and adjusted models. This consistent pattern was observed regardless of gender. Results of population-based data with over a median follow-up period of 20 years showed that CKD independently increases the risk of CV events in both men and women. However, our findings suggest that this elevated risk may not be substantially influenced by prolactin levels. Further investigation may be warranted to confirm these findings.