Abstract: Bone marrow transplantation (BMT) remains the only potentially curative treatment for patients with thalassemia major. However, most candidates for BMT do not have a suitable family donor. In order to evaluate whether BMT from an HLA‐matched unrelated volunteer donor can offer a probability of cure comparable to that obtained when the donor is a compatible sibling, we carried out a study involving 68 thalassemia patients transplanted in six Italian BMT Centers. Thirty‐three males and 35 females (age range, 2‐37 years; median age, 15) were transplanted from unrelated volunteer donors, all selected using high‐resolution molecular typing of both HLA class I and II loci. Fourteen patients were classified in risk class 1; 16 in risk class 2; and 38 in risk class III of the Pesaro classification system. Nine patients (13%) had either primary or secondary graft failure. Fourteen patients (20%) died from transplant‐related causes. Grade II‐IV acute graft‐versus‐host disease (GVHD) developed in 24 cases (40%), and chronic GVHD in 10 cases (18%). Overall survival (OS) in the cohort of 68 patients was 79.3% (CI 67‐88%), whereas the Kaplan‐Meier estimates of disease‐free survival (DFS) with transfusion independence was 65.8% (CI 54‐77%). In the group of 30 thalassemic patients in risk classes 1 and 2, the probability of OS and DFS were 96.7% (CI 90‐100%) and 80.0% (CI 65‐94%), respectively, whereas in the 38 patients in class 3 OS was 65.2% (CI 49‐80%) and DFS was 54.5% (CI 38‐70%). These data show that when donor selection is based on stringent compatibility criteria, the results of unrelated transplantation in thalassemia patients are comparable to those obtained when the donor is a compatible sibling.