Stenotrophomonas maltophilia is an important nosocomial pathogen with intrinsic multi-drug resistance. This retrospective study reviewed 84 episodes of S. maltophilia bacteremia over a 4-year period from July 1999 to September 2003. Stenotrophomonas maltophilia bacteremia was hospital-acquired in 64 patients (76%), and developed after prolonged hospitalization in 48 (57%). Seventy patients (83%) had a central venous catheter (CVC), 64 (76%) had prior antibiotic therapy, 55 (65%) had underlying malignancy, and 43 (51%) were receiving immunosuppressive therapy. Twenty seven percent of the episodes of bacteremia had polymicrobial isolates. The overall and bacteremia-related mortality rates were 44% and 33%, respectively. Forty six percent of the bacteremia-related mortality occurred within 3 days after onset of symptoms. The most common sources of bacteremia were respiratory tract (33%) and CVC (31%), while the source of the bacteremia was unknown in 26% of episodes. The most effective antibiotics in vitro were trimethoprim-sulfamethoxazole, ciprofloxacin, chloramphenicol, and ceftazidime; however, a trend of increasing drug resistance in these agents was identified over the study period. On univariate analysis, nosocomial bacteremia, long-lasting neutropnenia (>10 days), bacteremia originating from the respiratory tract, shock, low serum albumin level (<3 g/dL), and thrombocytopenia (platelet count <100,000/mm3) were significantly related to mortality (p<0.05). Among these variables, shock and thrombocytopenia were independent factors associated with mortality. In contrast, patients with CVC-related bacteremia had a lower mortality rate (odds ratio, 0.04; p<0.001). Patients treated with appropriate antibiotics had a lower mortality rate, but this difference was not significant (p=0.477). In S. maltophilia bacteremia, careful evaluation of CVC was important for identifying the source of bacteremia and predicting prognosis. The source of bacteremia and condition of patients at presentation were the major factors influencing prognosis.