There is debate regarding the correlation between in vitro susceptibility testing and clinical response to therapy for Bacteroides bacteremia. We conducted a prospective multicenter observational study of 128 patients with bacteroides bacteremia. Outcome was correlated with results of in vitro susceptibility testing of Bacteroides isolates recovered from blood and/or nonblood sites, determined with use of 3 end points: mortality at 30 days, clinical response (cure vs. failure), and microbiological response (eradication vs. persistence). The mortality rate among patients who received inactive therapy (45%) was higher than among patients who received active therapy (16%; P=.04). Clinical failure (82%) and microbiological persistence (42%) were higher for patients who received inactive therapy than for patients who received active therapy (22% and 12%, respectively; P=.0002 and.06, respectively). In vitro activity of agents directed at Bacteroides species reliably predicts outcome: the specificity was 97%, and positive predictive value was 82%. Antimicrobial susceptibility testing may be indicated for patients whose blood specimens yield Bacteroides species.