Diverticular disease and acute coronary syndrome (ACS) are common disorders that share several risk factors. Few researchers have evaluated the association between diverticular disease and ACS. We aimed to assess the risk of ACS in patients with diverticular disease. A nationwide retrospective cohort study was conducted by analyzing data from the National Health Insurance Research Database in Taiwan. All patients aged ≥20 years with a diagnosis of diverticular disease from January 1, 2000, to December 31, 2011, were included in this study. For comparison, patients without diverticular disease were randomly selected and matched with the study cohort at a 4:1 ratio according to age, sex, and the year of the diagnosis of diverticular disease. Patients with incomplete age or sex information and a history of cardiovascular diseases were excluded from the study. All patients were followed until an ACS event, withdrawal from the insurance program, or December 31, 2011. In this study, 52,681 patients with diverticular disease and 210,724 patients without diverticular disease were included. Men accounted for 56.1% of patients and 57.8% of patients were ≥50 years old. The overall incidence density of ACS in patients with diverticular disease (45.5 per 10,000 person-years) was significantly higher than in those without diverticular disease (30.3 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.23 (95% confidence interval [CI], 1.14-1.32) after adjustment for age, sex, and comorbidities. The cumulative incidence of ACS in patients with diverticular disease was significantly higher than that in the control cohort (log-rank test, P < 0.001). The adjusted HRs for the development of ACS were 1.25 (95% CI, 1.15-1.37) and 1.19 (95% CI, 1.07-1.32) in patients with diverticulitis and diverticulosis, respectively. The adjusted HRs of ACS in patients with diverticular disease additionally increased from 1.97 (95% CI, 1.73-2.23) in patients with 1 comorbidity to 5.51 (95% CI, 3.88-7.84) in those with ≥5 comorbidities. This large population-based retrospective study revealed an association between diverticular disease and ACS. Further research is warranted to determine the exact mechanism of the link between these diseases.