Limited data exist regarding the incidence and factors associated with outcome of invasive Pseudomonal infections in hematopoietic cell transplant (HCT). A retrospective analysis of cases of invasive Pseudomonas aeruginosa infection and factors associated with outcome was performed. P. aeruginosa invasive infection occurred in 95 of 5772 patients (1.65%) a median of 63 days after HCT (range 5-1435). Only 28% of infections occurred during periods of neutropenia (absolute neutrophil count<500 cells/mm(3)). Infection-attributable mortality during the initial episode of infection was 35.8%. Factors associated with initial mortality included the presence of a copathogen and high-dose steroid use. Ten (16.4%) of those who survived the initial infection experienced a recurrence of P. aeruginosa infection at a median of 9 days (range 3-17) after stopping antibiotics and 60% of those died as a result of recurrent infection a median of 1 day (range 1-7) after onset of recurrence. Grade 3-4 graft-versus-host disease was associated with a higher risk of recurrent infection. The risk of recurrence was not influenced by the presence of copathogens. Thus, invasive P. aeruginosa infections are associated with high recurrence rates and mortality in this immunocompromised population. Aggressive attempts to reduce immunosuppression and to treat copathogens may help during the initial infection.