Background: Data looking at the first 48-hours of hospitalization for acute pancreatitis shows that lung injury predicts mortality. The objective of this study was to test if early respiratory compromise in the ED predicts mortality in acute pancreatitis. We secondarily assessed the addition of the quick sequential organ failure assessment (qSOFA) in predicting mortality. Methods: We performed a retrospective observational study across 8 EDs and 5 hospitals that was inclusive of consecutive adult patients hospitalized for acute pancreatitis. We excluded patients with lipase levels \u3c 3-times the upper limit of the normal laboratory range. The primary outcome was inpatient mortality. We performed univariate and multivariate logistic regression to determine clinical predictors of these outcomes, in which the main variable of interest was respiratory compromise defined by an initial ED SPO2 ≤ 92%. We further combined key ED variables to derive an area under the curve (AUC) for predicting mortality. Results: The study included 2,090 patients, of whom 51.5% were female and the mean age was 55.5 (SD 17.5) years. The median presenting lipase was 976 u/ L (IQR 281 - 2500). Death was uncommon (n=34, 1.6%). In univariate analysis, highly significant predictors of mortality were SPO2 ≤ 92%, qSOFA score, and low albumin. Patients with a presenting SPO2 ≤ 92% had 9.2% vs. 1.3% mortality (OR 7.5, 95% CI 3.1 - 17.7). Those with a qSOFA score ≥ 2 had 9.8% vs. 1.3% mortality (OR 8.6, 95% CI 3.9 - 18.9). Adjusting for age, gender, race, leukocytosis, hematocrit, and major comorbidities, qSOFA ≥ 2 remained a significant predictor of mortality (OR 2.6, 95%CI 1.7 - 4.1, p\u3c0.001). Low albumin (OR 2.7, 95% CI 1.2 - 6.2, p=0.02) and SPO2 ≤ 92% (OR 2.6, 95% CI 1.0-7.1, p=0.05) also remained significant predictors. By combining qSOFA with the presence of low albumin or SPO2 ≤ 92% into a novel ED acute pancreatitis score (EDAPS), the EDAPS score had good accuracy for predicting mortality (AUC 0.80, 95% CI 0.72-0.89). Conclusion: Across a large cohort of patients admitted for acute pancreatitis, mortality is markedly lower than previous data has shown. Independent predictors of mortality present in the ED include low albumin, SPO2 ≤ 92%, and a qSOFA score ≥ 2