beta-Thalassemia major (beta-TM) has become a public health problem in mainland China. Hematopoietic stem cell transplantation (HSCT) has remained the only cure for beta-TM in mainland China since 1998. This multicenter retrospective study provides a comprehensive review of the outcomes of 50 pediatric patients with beta-TM who received HSCT between 1998 and 2009 at five centers in mainland China. Both related (n = 35) and unrelated donors (n = 15) with complete human leukocyte antigen matches were included. The stem cell sources included bone marrow (BM), peripheral blood stem cells, umbilical cord blood (UCB) and a combination of BM and UCB or a combination of BM and peripheral blood stem cells from a single sibling donor. The probabilities of 5-year overall survival (OS) and thalassemia-free survival (TFS) after the first HSCT were 83.1 and 67.3%, respectively. Graft failure (GF) occurred in 17 patients. Univariate analyses showed that umbilical cord blood transplantation (UCBT) was one of the potential risk factors for decreased OS (P = 0.051), and that UCBT (P = 0.002) was potentially related to TFS. GF incidence was distinct between the UCBT and non-UCBT groups (P = 0.004). Four cases of UCB-BM combined transplantation led to decreased risks of mortality and recurrence. In the UCBT group, related donor transplantation produced more favorable results than unrelated donor transplantation in OS (P = 0.009) but not in TFS (P = 0.217). GF was the primary cause of UCBT failure. Though UCBT from related donors was not favorable, the combined transplantation of UCB and BM could improve the prognosis of UCBT.