To determine whether the quick Sequential Organ Failure Assessment (qSOFA) retains predictive validity in patients with Enterobacteriaceae sepsis that all received appropriate initial antimicrobial therapy.Retrospective cohort at Barnes-Jewish Hospital including individuals with Enterobacteriaceae sepsis receiving appropriate initial antimicrobial therapy between 6/2009-12/2013. Outcomes were compared according to qSOFA score and sepsis classification.We identified 510 patients with Enterobacteriaceae sepsis; 67 (13.1%) died. Mortality was higher in patients with qSOFA scores of 2 or 3 than those with scores of 0 or 1 (13.3% and 42.4% versus 5.1% and 1.8%). In multivariate logistic regression analysis, altered mental status (AMS) alone or qSOFA score≥2 were both predictors of mortality with odds ratios of 8.01 and 5.39, respectively. Regardless of sepsis severity, non-survivors were significantly more likely to have AMS than survivors. Sepsis severity, qSOFA, and AMS had comparable predictive validity for mortality.Our results support qSOFA score, AMS, and sepsis severity as acceptable bedside tools for prognostication during initial clinical assessment in patients with sepsis. qSOFA retained its predictive validity in this cohort, suggesting that appropriate initial antimicrobial therapy is not an effect modifier for mortality when using qSOFA for prognostication.