Acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) may be accompanied by the deterioration of cardiovascular comorbidities, as evidenced by the increased incidence of acute cardiovascular events.Whether preceding AE might be associated with mortality of cardiovascular events remains unknown.Using a health insurance research database in Taiwan, we identified patients with COPD who experienced first-time acute myocardial infarction (AMI; n=26,442), ischemic stroke (n=54,959) and intracranial hemorrhage (ICH; n=14,893) over a 13-year period. In each cohort, 4,356, 6,655 and 1,727 patients, respectively, had been hospitalized for AE within the previous year before the index cardiovascular events, and COPD patients without hospitalized AE constituted the controls. Odds ratios (ORs) of 90-day mortality and hazard ratios (HRs) of overall mortality during follow-up in relation to hospitalized AE and the frequency of hospitalized AEs (i.e., 1 and ≥2 hospitalized AEs) were estimated with adjustment for potential confounders.Hospitalized AE was independently associated with 90-day mortality of AMI (OR=1.33, 95% confidence interval [CI] 1.24-1.43), ischemic stroke (OR=1.46, 95% CI 1.36-1.56) and ICH (OR=1.19, 95% CI 1.06-1.32). Hospitalized AE was associated with overall mortality of AMI (HR=1.23, 95% CI 1.19-1.27), ischemic stroke (HR=1.29, 95% CI 1.26-1.33) and ICH (HR=1.19, 95% CI 1.13-1.26). In addition, compared with controls, patients with more frequent hospitalized AEs exhibited significant trends at higher risk of 90-day and overall mortality of AMI, ischemic stroke and ICH. Finally, these results were consistent with propensity score matching-based estimates.Preceding hospitalized AE is associated with 90-day and overall mortality of cardiovascular events in COPD.