BACKGROUND: Early identification of patients at risk of developing acute lung injury (ALI) is critical for potential preventive strategies. We aimed to derive and validate an acute lung injury prediction score (EDLIPS) in a multicenter sample of emergency department (ED) patients. METHODS: We performed a subgroup analysis of 4,361 ED patients enrolled in the previously reported multicenter observational study. ED risk factors and conditions associated with subsequent ALI development were identified and included in the EDLIPS model. Scores were derived and validated using logistic regression analyses. The model was assessed with the area under the receiver-operating curve (AUC) and compared to the original LIPS model (derived from a population of elective high-risk surgical and ED patients) and the Acute Physiology and Chronic Health Evaluation (APACHE II) score. RESULTS: The incidence of ALI was 7.0% (303/4361). EDLIPS discriminated patients who developed ALI from those who did not with an AUC of 0.78 (95% CI 0.75, 0.82), better than the APACHE II AUC 0.70 (p ≤ 0.001) and similar to the original LIPS score AUC 0.80 (p = 0.07). At an EDLIPS cutoff of 5 (range -0.5, 15) positive and negative likelihood ratios (95% CI) for ALI development were 2.74 (2.43, 3.07) and 0.39 (0.30, 0.49), respectively, with a sensitivity 0.72(0.64, 0.78), specificity 0.74 (0.72, 0.76), and positive and negative predictive value of 0.18 (0.15, 0.21) and 0.97 (0.96, 0.98). CONCLUSION: EDLIPS may help identify patients at risk for ALI development early in the course of their ED presentation. This novel model may detect at-risk patients for treatment optimization and identify potential patients for ALI prevention trials.