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Acute lung injury (ALI) may complicate thoracic surgery and is a major contributor to postoperative mortality. We analyzed risk factors for ALI in a cohort of 879 consecutive patients who underwent pulmonary resections for non-small cell lung carcinoma. Clinical, anesthetic, surgical, radiological, biochemical, and histopathologic data were prospectively collected. The total incidence of ALI was 4.2% (n = 37). In 10 cases, intercurrent complications (bronchopneumonia, n = 5; bronchopulmonary fistula, n = 2; gastric aspiration, n = 2; thromboembolism, n = 1) triggered the onset of ALI 3 to 12 days after surgery, and this was associated with a 60% mortality rate (secondary ALI). In the remaining 27 patients, no clinical adverse event preceded the development of ALI—0 to 3 days after surgery—that was associated with a 26% mortality rate (primary ALI). Four independent risk factors for primary ALI were identified: high intraoperative ventilatory pressure index (odds ratio, 3.5; 95% confidence interval, 1.7–8.4), excessive fluid infusion (odds ratio, 2.9; 95% confidence interval, 1.9–7.4), pneumonectomy (odds ratio, 2.8; 95% confidence interval, 1.4–6.3), and preoperative alcohol abuse (odds ratio, 1.9; 95% confidence interval, 1.1–4.6). In conclusion, we describe two clinical forms of postthoracotomy ALI: 1) delayed-onset ALI triggered by intercurrent complications and 2) an early form of ALI amenable to risk-reducing strategies, including preoperative alcohol abstinence, lung-protective ventilatory modes, and limited fluid intake.