Objective:Almost half of the patients with septic shock develop acute lung injury (ALI). The understanding why some patients do and others do not develop ALI is limited. The objective of this study was to test the hypothesis that delayed treatment of septic shock is associated with the development of ALI. Design:Observational cohort study. Setting:Medical intensive care unit in a tertiary medical center. Patients:Prospectively identified patients with septic shock who did not have ALI at the outset, excluding those who denied research authorization. Measurements and Main Results:High frequency cardio-respiratory monitoring, arterial gas analysis, and portable chest radiographs were reviewed to identify the timing of ALI development. Risk factors present before ALI development were identified by review of electronic medical records and analyzed in univariate and multivariate analyses. Seventy-one of 160 patients (44%) developed ALI at a median of 5 (range 2–94) hours after the onset of septic shock. Multivariate logistic regression analysis identified the following predictors of ALI development: delayed goal-directed resuscitation (odds ratio [OR] 3.55, 95% confidence interval [CI] 1.52–8.63, p = .004), delayed antibiotics (OR 2.39, 95% CI 1.06 −5.59, p = .039), transfusion (OR 2.75, 95% CI 1.22–6.37, p = .016), alcohol abuse (OR 2.09, 95% CI .88−5.10, p = 0.098), recent chemotherapy (OR 6.47, 95% CI 1.99−24.9, p = 0.003), diabetes mellitus (OR .44, 95% CI .17−1.07, p = .076), and baseline respiratory rate (OR 2.03 per sd, 95% CI 1.38−3.08, p < .001). Conclusion:When adjusted for known modifiers of ALI expression, delayed treatment of shock and infection were associated with development of ALI.