The use of unmanipulated graft is increasingly adopted in the setting of allogeneic hematopoietic stem cell transplantation from haploidentical family donors (haplo-SCT) in acute leukemia (AL). We analyzed the outcome of 229 adult patients with de novo AL, who received an unmanipulated haploidentical transplant as their first allo-SCT between 2007 and 2011. Median follow-up was 30 months. Disease status at transplant was: first complete remission (CR1) for 77, second CR (CR2) for 56, and advanced for 96 patients. One hundred and seventy-one patients received in vivo T-cell depletion by monoclonal antibodies (75%). The 60-day cumulative incidence (CI) of engraftment was 93±2%. The 100-day CI of acute graft-versus-host disease (GvHD) was 32±3% for grade II-IV, 12±3% for grade III-IV. The 3-year CI of chronic GvHD was 34±3%. The 3-year CI of non-relapse mortality was 31±4% with in vivo T-cell depletion and 17±5% without. At 3 years, for patients transplanted in CR1, CR2 or advanced disease leukemia-free survival was 44±6, 42±7 and 12±3%, overall survival was 55±6, 51±7 and 14±4% and CI of relapse was 32±6, 24±6 and 61±5%, respectively. These data suggest that unmanipulated haplo-SCT is a valid treatment option for adult AL patients in complete remission lacking a matched donor.