Twenty-two adult acute lymphoblastic leukemia (ALL) patients (21 of 22 in complete remission [CR]) received reduced- intensity conditioning followed by allogeneic transplantation. All patients were high risk. After a uniform preparative regimen (fludarabine 40 mg/m 2 × 5, cyclophosphamide 50 mg/kg, 200 cGy total body irradiation), patients received either matched related (n = 4) or umbilical cord (n = 18) donor grafts. All patients reached neutrophil engraftment and 100% donor chimerism (median, days 10 and 23, respectively). Overall survival, treatment-related mortality (TRM) and relapse were 50% (95% confidence interval [CI], 27%-73%), 27% (95% CI, 9%-45%), and 36% (95% CI, 14%-58%) at 3 years, respectively. There were no relapses beyond 2 years. The cumulative incidence of acute and chronic graft-versus-host disease was 55% and 45%. Hematopoietic cell transplantation in CR1 (n = 14) led to significantly less TRM (8%, P <.04) and improved overall survival (81%, P <.01). For adults with ALL in CR, reduced intensity conditioning allografting results in modest TRM, limited risk of relapse, and promising leukemia-free survival. Clinical trial numbers are NCT00365287, NCT00305682, and NCT00303719.