Background: Recent studies have shown an association between CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack (TIA), vascular disease, age 65 to 74 years, sex category) score and outcome of acute myocardial infarction, stroke, and chest pain. As pneumonia can affect the cardiovascular system, this study aimed to investigate the performance of the CHA2DS2-VASc score for major adverse cardiovascular events (MACEs) risk stratification in patients with pneumonia. Methods: A retrospective population-based cohort study including 61,843 patients with pneumonia. These patients were divided into two cohorts that were stratified based on the presence or absence of underlying atrial fibrillation (AF). We calculated the CHA2DS2-VASc score and incidence density rates of MACEs in each cohort. Cox regression was conducted to calculate hazard ratio of MACEs in pneumonia patients. The diagnostic performance of CHA2DS2-VASc with regard to MACEs was tested using the receiver operator characteristic curve. Results: Pneumonia patients with higher CHA2DS2-VASc score were more likely develop MACEs in both the AF and non-AF groups. In the AF group, the areas under the curve (AUC), sensitivity, and specificity were 0.824 (0.7773–0.8708), 0.7, and 0.84 respectively. In the non-AF group, the AUC, sensitivity, and specificity were 0.8185 (0.8152–0.8217), 0.75, and 0.83 respectively. Conclusions: The CHA2DS2-VASc score showed good performance in the prediction of MACE in patients with pneumonia.