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Hysterectomy is a common procedure for benign pathologies of the uterus. Reduced production of estrogen following hysterectomy has been reported. Yet the association between hysterectomy and coronary artery disease (CAD) risk remains controversial. The aim of this study was to investigate the effect of hysterectomy on the risk of CAD; calculations were adjusted for traditional risk factors.This study used a 1 million patient cohort of the Taiwan National Health Insurance database and included a total of 7331 women who received hysterectomy from 2000 to 2013. We randomly selected a control group composed of 29,324 women without hysterectomy by 1:4 matching the age (exact year) with the hysterectomy group.The mean (standard deviation) age was 43.5 ± 4.0 in the hysterectomy and 43.6 ± 4.0 in the control group. A total of 1986 CAD cases developed in both groups during a median follow-up of 7 years. Significant differences were observed in CAD incidence in the hysterectomy versus control group (9.82 vs. 7.17/1000 person-years, P < .001, adjusted hazard ratio = 1.31 [95% confidence interval: 1.18–1.45]).We found a significant association between hysterectomy and CAD, even after adjustment for baseline CAD risk factors.