We report on the incidence, risk factors, and outcome of late Staphylococcus aureus bacteremia (SAB) in a cohort of 709 adult and pediatric patients at Memorial Sloan-Kettering Cancer Center between September 1999 and December 2006. The SAB cases were identified by prospective surveillance and examination of a computerized database. Late SAB was defined as SAB occurring > 50 days post-hematopoietic stem cell transplantation (HSCT). A nested case-controlled study was conducted to identify predictors of late SAB. The incidence of late SAB was 6/100,000 patient-days. The median time from stem cell infusion to incident blood culture was 137 days (range, 55 to 581 days). Eighty-four percent of the cases were community acquired; 40% involved a focal infection. Bacteremia was persistent (>3 days) despite removal of endovascular access in > 50% of cases. Risk factors for late SAB were acute graft-versus-host disease (aGVHD) flare, acute or chronic skin GVHD (cGVHD), corticosteroid use, liver dysfunction, and prolonged hospital length of stay (LOS) post-HSCT. In multivariate models, skin GVHD (P = .002) and LOS (P = .02) remained significant. The median survival post-SAB was 135 days (range, 1 to 1765 days). Late SAB occurred mainly in the setting of GVHD or corticosteroid therapy. Clinical manifestations were highly variable. Multiple comorbidities, indicated by organ dysfunction and hospitalization, likely contributed to persistence and increased morbidity and mortality. We recommend a high index of suspicion and empiric antistaphylococcal treatment pending culture results in high-risk patients undergoing HSCT.