Despite significant improvements in the supportive care, sickle cell disease (SCD) leads to significant morbidity and mortality. Allogeneic hematopoietic stem cell transplantation (HSCT), the only curative option, is limited due to matched donor availability. This could be met with T-cell-depleted haploidentical HSCT. Twenty advanced-stage SCD patients, median age 15 years, and 9 patients, median age 14 years, were transplanted with CD3/CD19- or TCRαβ/CD19-depleted grafts and from matched sibling donors (MSDs). The conditioning consisted of ATG, thiotepa, fludarabine, and treosulfan. The median follow-up in the T-haplo-HSCT and the MSD patients was 21 (9-62) and 25 (7-60) months, respectively. The OS in the T-haplo-HSCT and MSD was 90% and 100%, respectively. In the T-haplo-HSCT group, two patient succumbed to a CMV pneumonitis and a macrophage activation syndrome (MAS). One patient in the T-haplo-HSCT group requires renal replacement therapy because of BK virus nephritis. None developed grade III-IV acute GvHD. In the T-haplo-HSCT and in the MSD, 20% and 22%, respectively, developed a mild or moderate chronic GvHD. These results demonstrate the feasibility, safety, and efficacy of T-haplo-HSCT also for adult advanced stage SCD patients.