Background. Due to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination of cyclophosphamide and antithymocyte globulin. We report the long-term follow-up of patients who underwent hematopoietic stem cell transplantation from an HLA-matched sibling donor after this conditioning regimen.Design and Methods. We analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following cyclophosphamide (200mg/kg) and antithymocyte globulin (2.5 mg/kg/day x 5 days).Results. The median age was 21 years [range: 4-43], 41 were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II-IV GvHD was 23% (95%CI, 13-34) and 18 developed chronic GvHD (cumulative incidence 32% at 72 months, 95% CI, 20-46). In multivariate analysis, higher number of infused CD3 cells was associated with an increased risk of developing chronic GvHD (p=0.017). With a median follow-up of 73 months [8-233], the estimated 6-years overall survival was 87% (95% CI 78 to 97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin lymphoma) during follow-up.Conclusions. Cyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction.Key words: Hematopoietic stem cell transplantation, severe aplastic anemia, long-term outcomes.