Postoperative atrial fibrillation (POAF) is the most frequent complication of cardiac surgery and is associated with increased morbidity and mortality. Pharmacologic prophylaxis is the main method of preventing POAF but needs to be targeted to patients at high risk of developing POAF. The CHA2DS2-VASc scoring system is a clinical guideline for assessing ischemic stroke risk in patients with atrial fibrillation. The present study evaluated the utility of this scoring system in predicting the risk of developing de novo POAF in cardiac surgery patients.A total of 2385 patients undergoing cardiac surgery at our institution from 2008–2014 were identified for analysis. Each patient was assigned a CHA2DS2-VASc score and placed into a low- (score of 0), intermediate- (1), or high-risk (≥2) group. A multivariate regression model was created to control for known risk factors of atrial fibrillation.POAF occurred in 380 of 2385 patients (15.9%). Mean CHA2DS2-VASc scores among patients with POAF and without POAF were 3.6 ± 1.7 and 2.8 ± 1.7, respectively (P < 0.0001). Using multivariate analysis, as a patient's CHA2DS2-VASc score rose from 0–9, the risk of developing POAF increased from 8.2%–42.3%. Each point increase was associated with higher odds of developing POAF (adjusted odds ratio, 1.27; 95% confidence interval, 1.18–1.36, P < 0.0001). Compared with low-risk patients, patients in the high-risk group were 5.21 times more likely to develop POAF (P < 0.0001).The CHA2DS2-VASc algorithm is a simple risk-stratification tool that could be used to direct pharmacologic prophylaxis toward patients most likely to experience POAF.