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Our objective was to compare in-hospital mortality among emergency department (ED) patients meeting trial-based criteria for septic shock based upon whether presenting with refractory hypotension (systolic blood pressure < 90 mm Hg after 1 L intravenous fluid bolus) versus hyperlactatemia (initial lactate ≥ 4 mmol/L).We conducted a retrospective cohort analysis by chart review of ED patients admitted to an intensive care unit with suspected infection during 1 August 2012–28 February 2015. We included all patients with body fluid cultures sampled either during their ED stay without antibiotic administration or within 24 h of antibiotic administration in the ED. We excluded patients not meeting criteria for either refractory hypotension or hyperlactatemia. Trained chart abstractors blinded to the study hypothesis double entered data from each patient's record including demographics, clinical data, treatments, and in-hospital mortality. We compared in-hospital mortality among patients with isolated refractory hypotension, isolated hyperlactatemia, or both. We also calculated odds ratios (ORs) via logistic regression for in-hospital mortality based on presence of refractory hypotension or hyperlactatemia.Of 202 patients included in the analysis, 38 (18.8%) died during hospitalization. Mortality was 10.9% among 101 patients with isolated refractory hypotension, 24.4% among 41 patients with isolated hyperlactatemia, and 28.3% among 60 patients with both (p = 0.01). Logistic regression analyses yielded in-hospital mortality OR for refractory hypotension of 1.3 (95% CI 0.5–3.8) versus OR for hyperlactatemia of 2.9 (95% CI 1.2–7.4).Hyperlactatemia appears associated with higher in-hospital mortality compared to refractory hypotension among ED patients with septic shock.