Objective: To investigate the characteristics, risk factors and outcomes of thalassemia major (TM) children with pericardial effusion (PE) after allo-geneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Clinical data of 446 TM children received allo-HSCT at Shenzhen Children's Hospital between January 2012 and December 2020 were analyzed retrospectively. Patients were divided into PE and non-PE group according to the occurrence of PE. Chi-square tests were used to investigate the risk factors that were associated with the development of PE. Kaplan-Meier method was used for survival analysis of the 2 groups. Results: Twenty-five out of 446 patients (5.6%) developed PE at a time of 75.0 (66.5, 112.5) days after allo-HSCT. Among these patients, 22 cases (88.0%) had PE within 6 months after allo-HSCT and 19 patients (76.0%) had PE within 100 days after allo-HSCT. The diagnoses of PE were confirmed using echocardiography. Pericardial tamponade was observed in only 1 patient, who later undergone emergency pericardiocentesis. The rest of patients received conservative managements alone. PE disappeared in all patients after treatment. Risk factors that were associated with the development of PE after allo-HSCT included the gender of patients, the type of transplantation, the number of mononuclear cells (MNC) infuse, pulmonary infection after HSCT and transplantation associated thrombotic microangiopathy (TA-TMA) (χ²=3.99, 10.20, 14.18, 36.24, 15.03, all P<0.05). In 239 patients that received haploidentical HSCT, the development of PE was associated with the gender of patients, pulmonary infection after HSCT and TA-TMA (χ²=4.48, 20.89, 12.70, all P<0.05). The overall survival rates of PE and non-PE groups were 96.0% (24/25) and 98.6% (415/421). The development of PE was not associated with the overall survival of TM children after allo-HSCT (χ²=1.73, P=0.188). Conclusions: PE mainly develop within 100 days after allo-HSCT in pediatric TM recipients. Haploidentical grafts, female gender, pulmonary infection after HSCT and TA-TMA are the main risk factors associated with PE development after transplant. However, the presence of PE don't have a significant impact on the outcomes of pediatric TM patients after allo-HSCT.