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STUDY OBJECTIVE The quick sequential organ failure assessment (qSOFA) was proposed to identify infected patients at risk for mortality, an indication of sepsis, in non-intensive care unit settings. This study tests whether qSOFA improves physician prediction of mortality among infected Emergency Department (ED) patients. METHODS We performed a secondary analysis of a prospective, observational study of potentially septic ED patients, conducted between two urban, academic medical centers, from July 2016 - December 2017. We enrolled ED patients with 1) two or more systemic inflammatory response syndrome criteria and severe sepsis qualifying organ dysfunction, 2) systolic blood pressure <90 mmHg, or 3) lactate ≥ 4.0 mmol/L. Infectious etiology was adjudicated retrospectively by paired physician review. We excluded non-infected patients. Treating ED physicians submitted judgment for in-hospital mortality (0-100%) at hospital admission, and qSOFA was calculated retrospectively using ED data. The primary outcome was in-hospital mortality within 28 days. We used logistic regression to predict mortality using 1) physician judgment, 2) qSOFA, and 3) combined physician judgment and qSOFA. To assess differences between models, 95% confidence intervals for area under the curve (AUC) were derived by bootstrapping with 1,000 iterations. RESULTS Of 405 patients meeting inclusion criteria, 195 (48.1%) were determined to have infection and analyzed. Of analyzed patients, 16 (8.2%) suffered in-hospital mortality within 28 days. Analyzed patients had a mean age of 58.3 (SD 16.5) years and 78 (40%) were female. qSOFA alone (AUC 0.63; 95%CI: 0.53-0.73) was not superior to unstructured physician judgment (AUC 0.80; 0.70-0.89) when predicting 28-day in-hospital mortality with mean AUC difference 0.17 (0.07-0.28) across bootstrapped datasets. Combining qSOFA with physician judgment (AUC 0.79; 0.69-0.89) did not improve performance compared to physician judgment alone. CONCLUSION When predicting 28-day in-hospital mortality among infected ED patients, qSOFA did not outperform or improve physician judgment.