Objectives Ischemic stroke is a severe complication following cardiac surgery, but its risk factors remain to be further studied. This study assesses the predictive value of CHADS2 scores for perioperative ischemic stroke among patients undergoing mitral valve replacement surgery. Methods The data on 805 atrial fibrillation patients (52.4% female; age 53.7±10.5 years) undergoing mitral valve replacement between 2005 and 2014 were collected and analyzed. CHADS2 scores were used to stratify the perioperative ischemic stroke risk. Multivariate analysis by logistic regression was performed to determine the variables used to predict postoperative stroke. Results CHADS2 score were as follows: 0 point in 493 cases (61.2%), 1 point in 185 cases (23.0%), 2 points in 92 cases (11.4%), 3 points in 26 cases (3.2%) and 4 points in 9 cases (1.1%). A total of 14 cases (1.7%) had stroke during hospital stay. 16 patients died during hospitalization, the mortality rate was 2%. Stroke occurred in 6 cases among 0-point patients (incidence rate 1.2%), 2 case among the 1-point patients (1.1%), 3 cases among the 2-point patients (3.3%), 2 cases among the 3-point patients (7.7%), and 1case among 4-point patients (11.1%). Patients with CHADS2 score ≥2 , compared with patients with CHADS2 score < 2, had higher incidence of stroke during hospitalization period(4.6% vs.1.2%; P = 0.006). Multivariate logistic regression analysis showed that the CHADS2 score ≥2 (OR, 4.063; 95% CI, 135.5~12.188; P=0.012) and application of recombinant human coagulation factor VIIa (OR, 11.832; 95% CI, 2.931~47.572; P=0.001) were independent risk factors for stroke during hospitalization period. Conclusion There is an increased risk of stroke in mitral valve replacement patients with higher CHADS2 score. CHADS2 score ≥2 is an independent risk predictors of postoperative stroke. The CHADS2 score is useful to predicate perioperative ischemic stroke in atrial fibrillation patients undergoing mitral valve replacement surgery and worth further study