The aim of the study is to evaluate the risk of heart disease in individuals who underwent cholecystectomy. This was a retrospective cohort study using the National Health Insurance Service database of South Korea. A total of 146,928 patients who underwent cholecystectomy and 268,502 age- and sex-matched controls were compared. Multivariate Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for heart disease after cholecystectomy. In results, a previous history of cholecystectomy increased the risk of heart disease (congestive heart failure [CHF], myocardial infarction [MI], atrial fibrillation [AF]) (adjusted HR [aHR]: 1.40, 95% CI: [1.36-1.44]). The increased risk was particularly seen for CHF (1.22 [1.16-1.29]) but not for MI and AF (p > 0.05). In the subgroup analyses, cholecystectomy was associated with an increased risk of MI in patients aged <65 years (1.49 [1.16-1.92] and 1.18 [1.05-1.35] in patients aged 40-49 and 50-64 years, respectively), but not in those aged ≥ 65 years (0.932 [0.838-1.037]). Moreover, the risk of MI was increased in patients without diabetes mellitus (DM) (1.16 [1.06-1.27]); however, it was decreased in patients with DM (0.83 [0.72-0.97]). In contrast, cholecystectomy did not modify the risk of AF in the subgroup analyses (all p > 0.05). In conclusion, a history of cholecystectomy is associated with an increased risk of CHF. Cholecystectomy may increase the risk of MI in the younger population without DM. These findings suggest that the alteration of bile metabolism and homeostasis might be potentially associated with the development of some heart diseases.