The study was to assess the relationship between antibiotic therapy and the outcome in intensive care unit (ICU) patients with Stenotrophomonas maltophilia bloodstream infection (BSI). ICU patients with monomicrobial S. maltophilia BSI from January 2004 to December 2019 were included and divided into two groups-those with- and without appropriate antibiotic therapy after BSI-for comparison. The primary outcome was the relationship between appropriate antibiotic therapy and 14-day mortality. The secondary outcome was the influence of different antibiotic therapies: levofloxacin- and trimethoprim-sulfamethoxazole (TMP/SMX)-containing regimens, on 14-day mortality. A total of 214 ICU patients were included. Patients received appropriate antibiotic therapy (n=133) after BSI had a lower 14-day mortality than those (n=81) without appropriate antibiotic therapy (10.5% vs. 46.9%, p<0.001). No difference on 14-day mortality between groups of patients by time of appropriate antibiotic therapy was observed (p>0.05). After a propensity score matching, the results is consistent that 14-day mortality were lower in patients with appropriate antibiotic therapy than those without appropriate antibiotic therapy (11.5% vs. 39.3%, p<0.001). Among patients with S. maltophilia BSI receiving appropriate antibiotic therapy, there was a trend levofloxacin-containing regimens is associated with lower mortality than TMP/SMX-containing regimens (HR 0.233, 95% CI 0.050-1.084, p=0.063). Appropriate antibiotic therapy was associated with decreased 14-day mortality in ICU patients with S. maltophilia BSI regardless of time. Levofloxacin-containing regimens may be better choice than TMP/SMX -containing regimens in treating ICU patients with S. maltophilia BSI.