Vancomycin-resistant enterococci (VRE) are common pathogens of bloodstream infections in the peritransplantation period. Linezolid is approved by the FDA for treating VRE infections, but has been associated with low rates of hematologic toxicity in the general population; thus, there are concerns about its potential myelotoxicity in the allogeneic hematopoietic stem cell transplantation (HSCT) setting. We examined the impact of linezolid treatment on the times to neutrophil and platelet engraftment in 33 patients who underwent HSCT. In this retrospective case-controlled study conducted from 2000 through 2007, cases received > or = 7 consecutive days of linezolid therapy, starting before day +8 post-HSCT. Controls received > or = 7 consecutive days of vancomycin therapy before day +8 and were matched to cases by age and conditioning regimen. The cumulative incidence function was used to estimate the probabilities for the times to neutrophil and platelet engraftment. A competing-risk regression model was used to determine whether times to engraftment differed for cases and controls. A total of 33 cases were compared with 33 controls. The median duration of treatment after stem cell infusion was 14 days (range, 7 to 34 days) for linezolid and 16 days (range, 8 to 33 days) for vancomycin. The rates of neutrophil and platelet engraftment were similar between the cases and controls. After adjusting for baseline characteristics, no difference in the times to neutrophil or platelet engraftment was seen between the 2 groups. Our findings demonstrate no adverse effect on the times to neutrophil or platelet engraftment with linezolid use. Larger prospective studies are needed to fully determine the hematologic safety of linezolid in patients undergoing HSCT.