OBJECTIVE: To characterize risk factors for Stenotrophomonas maltophilla bloodstream infection in oncology patients. DESIGN: A 3:1 case-control study. SETTING: Stem Cell Transplant and Leukemic Center at Barnes-Jewish Hospital (St. Louis), a 1,442-bed, tertiary-care teaching hospital with a 26-bed transplantation ward. METHOD: From June 1999 to April 2001, 13 patients with S. maltophilia bacteremia were compared with 39 control-patients who were on the transplantation unit on the same day as the case-patients' positive blood cultures. Information collected included patient demographics, medical history, history of transplantation, transplantation type, graft versus host disease, neutropenia, antibiotic use, chemotherapy, mucositis, diarrhea, the presence of central venous catheter(s), cultures, and concomitant infections. RESULTS: Significant risk factors for S. maltophilia bacteremia included severe mucositis (7 [53.8%] of 13 vs 8 [20.5%] of 39; P = .034), diarrhea (7 [53.8%] of 13 vs 8 [20%] of 39; P = .034), and the use of metronidazole (9 [69.2%] of 13 vs 8 [20.5%] of 39; P =.002). In addition, the number of antibiotics used (median, 9 vs 5; P < .001), duration of mucositis (median, 29 vs 15 days; P = .032), and length of hospital stay (median, 34 vs 22 days; P = .017) were significantly different between case- and control-patients. Nine S. maltophilia isolates tested by pulsed-field gel electrophoresis were found to be distinctly different CONCLUSION: Interventions to ameliorate the severity of mucositis, reduce antibiotic pressure, prevent diarrhea, and promote meticulous central venous catheter care may help prevent S. maltophilia bloodstream infection in oncology patients. The role of gastrointestinal tract colonization as a potential source of S. maltophilia bacteremia in oncology patients deserves further investigation.