Objective To evaluate the impact of valve replacement combined with epicardial left atrial appendage closure with high-risk heart valve disease complicated with atrial fibrillation on short-term outcome. Methods A total of 114 patients who underwent open-heart valve replacement surgery were selected as the research objects. All patients had HAS-BlED score≥3 and CHA2DS2-VASC score≥2 (female≥3). According to whether left atrial appendage was closed, patients were divided into group A (closed group, n=58) and group B (unclosed group, n=56). The operation indexes, cardiac function indexes, blood related factors and the incidence of cardiovascular adverse events after 6 months were observed in the two groups. Result sThe levels of C-reactive protein levels, brain natriuretic peptide, interleukin-1β, interleukin-6 and tumor necrosis factor-α of group A were lower than those of group B (P<0.05). The left atrial diameter and left ventricular end-diastolic diameter of the patients in combined surgery group were decreased (P<0.05), the ejection fraction was increased (P<0.05). The rates of incidence of cardiovascular adverse events occurrence to group B observed six months after operation were higher than those of group A (P<0.05). Conclusion Transepicardial left atrial appendage closure is safe and reliable, and has a good early postoperative effect after operation, which is conducive to the prevention of postoperative stroke.