Bone marrow transplantation (BMT) performance can be limited by a lack of ideal donors, and the role of alternative donor hematopoietic cell transplantation in thalassemia is not well established. Here we used a new treatment protocol (Pc 26.1) in 16 thalassemia patients to perform BMT using phenotypically HLA-identical or 1-antigen–mismatched relatives (related donors RDs). We compared these results with HLA-matched sibling (matched sibling donors MSDs) BMT in 66 patients. The entire RD group and 88% of MSD group had sustained engraftment. Rejection incidence was 0% in the RD and 12% (95% confidence interval 95% CI, 6%-21%) in MSD groups (P = .15), with respective thalassemia-free survival probabilities of 94% (95% CI, 63%-99%) and 82% (95% CI, 70%-89%) (P = .24). Transplant-related mortality was 6% (95% CI, 1%-26%) in the RD group and 8% (95% CI, 3%-16%) in the MSD group (P = .83). The intensified new protocol was not associated with increased nonhematologic toxicity. The present data show that the Pc 26.1 preparative regimen allows thalassemia patients to safely undergo BMT from RDs who are not HLA-matched siblings, with transplant outcomes similar to patients with MSD grafts. •A novel approach to BMT for thalassemia using related phenotypically matched or 1-antigen–mismatched donors improved transplant outcomes.•BMT from phenotypically matched or 1-antigen–mismatched donors is associated with a high thalassemia-free survival rate (94%).