The aim of this study was to determine potential risk factors for mortality in patients with nosocomial Stenotrophomonas maltophilia pneumonia. A retrospective, single-center, observational study. A 2400-bed tertiary teaching hospital in southern Taiwan. This retrospective study evaluated patients (age, at least 18 years) with nosocomial pneumonia (S. maltophilia isolated from respiratory culture) who were seen at Kaohsiung Chang Gung Memorial Hospital over a 3-year period. A total of 406 patients (64% male, mean age +/- standard deviation, 69.6 +/- 14.93 years; mean duration of hospital +/- standard deviation, 57.5 +/- 39.47 days) were included. Most index isolates (53.9%) were from the first sample cultured. Polymicrobial isolates were cultured from samples from 177 (43.6%) of the 406 study patients. The most common copathogen was Pseudomonas aeruginosa (53.11% of isolates). The all-cause hospital mortality rate was 42.6% (173 deaths among 406 patients). Survivors had a shorter time from admission to a positive index culture result than did nonsurvivors (26.1 vs 31.7 days; P = .04). Mortality was significantly higher among patients with malignancy (adjusted odds ratio [AOR], 2.48; 95% confidence interval [CI], 1.52-4.07; P < .001), renal disease (AOR, 2.6; 95% CI, 1.51-4.47; P = .001), intensive care unit stay (AOR, 1.72; 95% CI, 1.1-2.7; P = .018), and inadequate initial empirical antibiotic therapy (AOR, 2.17; 95% CI, 1.4-3.38; P = .001). S. maltophilia pneumonia is associated with a high mortality rate and is commonly associated with concomitant polymicrobial colonization or infection. Underlying comorbidities and inadequate initial empirical antibiotic therapy substantially account for increased mortality rates.