Background: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for patients with transfusion-dependent thalassemia (TDT), and the outcomes are influenced by multiple factors.Purpose: We retrospectively evaluated the clinical characteristics, risk factors, complications, and treatment outcomes in Thai patients aged <20 years using 30-year multicenter HSCT data. This study sought to evaluate the contributing factors affecting survival outcomes and complications, provide insights into the evolution of HSCT for TDT, and inform practice guidelines in developing countries. Methods: The outcomes of 266 HSCT procedures from related and unrelated donors in 249 Thai patients with TDT performed from 1988 to 2016 (median follow-up, 102 months) were analyzed. Results: The median age at HSCT was 6.9 years (range, 1−19 years). Most HSCT procedures used human leukocyte antigen-matched related donors (MRDs; 71.8%), with bone marrow serving as the primary graft source (69.5%). The thalassemia recurrence rate was 11.6%, whereas the mortality rate was 9.0%, primarily due to Gram-negative sepsis. The 5-year overall (OS) and event-free survival (EFS) were 91.3% and 81.0%, respectively. The outcomes did not differ significantly between MRDs and matched unrelated donors (MUDs: OS rate, 91.5% vs. 88.0%, P=0.52; EFS rate, 82.0% vs. 76.2%, P=0.45). Since 2000, advances in pre-HSCT transfusion, iron chelation, graft-versus-host disease prophylaxis, and supportive care have been implemented, with intravenous busulfan adopted after 2009. Over three periods (1988−1999, 2000−2009, and 2010−2016), the OS rate rose from 89.4% to 93.0% (P=0.74), and the EFS rate rose from 67.7% to 87.2% (P=0.01). Age ≤10 years was associated with better overall OS and EFS, although significance was limited to the earliest period. A multivariate analysis identified a pre-HSCT ferritin level >2,500 ng/mL, low CD34+ doses, and the use of oral busulfan conditioning as factors associated with unfavorable survival. Long-term complications, primarily endocrine disorders, affected 22.7% of survivors. Conclusion Our results broaden the donor pool by demonstrating comparable outcomes between MRD and MUD transplantation. Optimizing pretransplant care, such as regular pre-HSCT transfusion, adjusting conditioning intensity, and improving posttransplant supportive care, may mitigate age-related risks in older recipients.