INTRODUCTION: In lung cancer surgery, large tidal volume and elevated inspiratory pressure are known risk factors of acute lung (ALI). Mechanical ventilation with low tidal volume has been shown to attenuate lung injuries in critically ill patients. In the current study, we assessed the impact of a protective lung ventilation (PLV) protocol in patients undergoing lung cancer resection. METHODS: We performed a secondary analysis of an observational cohort. Demographic, surgical, clinical and outcome data were prospectively collected over a 10-year period. The PLV protocol consisted of small tidal volume, limiting maximal pressure ventilation and adding end-expiratory positive pressure along with recruitment maneuvers. Multivariate analysis with logistic regression was performed and data were compared before and after implementation of the PLV protocol: from 1998 to 2003 (historical group, n = 533) and from 2003 to 2008 (protocol group, n = 558). RESULTS: Baseline patient characteristics were similar in the two cohorts, except for a higher cardiovascular risk profile in the intervention group. During one-lung ventilation, protocol-managed patients had lower tidal volume (5.3 +/- 1.1 vs. 7.1 +/- 1.2 ml/kg in historical controls, P = 0.013) and higher dynamic compliance (45 +/- 8 vs. 32 +/- 7 ml/cmH2O, P = 0.011). After implementing PLV, there was a decreased incidence of acute lung injury (from 3.7% to 0.9%, P < 0.01) and atelectasis (from 8.8 to 5.0, P = 0.018), fewer admissions to the intensive care unit (from 9.4% vs. 2.5%, P < 0.001) and shorter hospital stay (from 14.5 +/- 3.3 vs. 11.8 +/- 4.1, P < 0.01). When adjusted for baseline characteristics, implementation of the open-lung protocol was associated with a reduced risk of acute lung injury (adjusted odds ratio of 0.34 with 95% confidence interval of 0.23 to 0.75; P = 0.002). CONCLUSIONS: Implementing an intraoperative PLV protocol in patients undergoing lung cancer resection was associated with improved postoperative respiratory outcomes as evidence by significantly reduced incidences of acute lung injury and atelectasis along with reduced utilization of intensive care unit resources.