Allogeneic hematopoietic stem cell transplantation (HSCT) is the recommended therapy for patients with relapsed acute myelogenous leukemia (AML), despite little evidence showing a survival benefit in patients who undergo HSCT versus chemotherapy alone. Because a prospective randomized trial addressing this issue is unlikely, we retrospectively reviewed all patients receiving initial salvage therapy for AML at M.D. Anderson Cancer Center between 1995 and 2004, focusing on patients undergoing HSCT or chemotherapy without HSCT as second salvage after first salvage failed to produce complete remission (CR) (group A) and patients in first salvage-induced CR (group B). Median survival was 5.1 months for HSCT (n=84) versus 2.3 months for chemotherapy (n = 200; P = .004) in group A and 11.7 months for HSCT (n = 46) versus 5.6 months for chemotherapy (n = 66; P < . 001) in group B. HSCT was associated with a survival benefit in each of 8 subgroups defined by age < or > or = 50, high-risk cytogenetics or not, and treatment in first salvage-induced CR or second salvage, and also in 5 of 6 subgroups defined by age < or > or = 50 years and duration of first CR (CR1) (primary refractory, CR1 < or = 36 weeks, CR1 > 36 weeks). Our data suggest that HSCT is preferable to chemotherapy alone in these patients with poor prognoses, with particular benefits noted in patients under age 50 years.