Background: Pericardial effusion has been known to develop commonly after orthotopic heart transplantation. However, previous studies have been inconclusive regarding etiology, necessity of drainage, and prognosis of these effusions. Methods: The medical records of 138 patients who underwent heart transplantation at Asan Medical Center from January 2000 to March 2009 were reviewed and analyzed. Pericardial effusion was defined by serial echocardiography. Patients who developed moderate to large effusion were considered to have significant effusion. Perioperative variables associated with the development of significant effusions were determined by logistic regression analysis. Results: Sixty-nine patients (50.0%) developed significant effusions after heart transplantation. 11 patients underwent pericardiostomy or pericardiocentesis during hospitalization because of hemodynamic compromise. The duration of significant effusions was 14.6짹12.8 months (range: 0.3 to 72). 5 patients developed postoperative pericardial constriction. Relatively young age (odds ratio 0.961, 95% confidence interval 0.931 to 0.991, p=0.011) and poor preoperative functional capacity (NYHA class IV; odds ratio 2.325, 95% confidence interval 1.126 to 4.800, p=0.023) were associated with occurrence of significant effusions. However, recipient���s weight, the difference in left ventricular mass, immunosuppressive agents, CMV infection, and the frequency of rejection were not associated with the development of them. Patients with significant effusions had higher chance of pericardial drainage and postoperative constriction. However, no intervention was performed after hospitalization in patients with long-lasting effusion (duration > 12 months). There was no difference in duration of hospital/ICU stay or mortality between patients with and without significant effusions. Conclusion: Postoperative significant effusions developed more frequently and lasted for a long time after heart transplantation compared to previous data. The prediction of them is still challenging. However, clinical course was benign even though the amount seemed to be significant.