Acute lung injury/acute respiratory distress syndrome (ALI / ARDS) is the most serious pulmonary complication after lung resection. This study investigated the incidence and outcome of patients with ALI / ARDS who required mechanical ventilation within one week of undergoing pneumonectomy for primary lung cancer and analysed the risk factors. We retrospectively reviewed the medical records of 146 patients who underwent pneumonectomy for primary lung cancer between May 2001 and April 2006. Preoperative, perioperative and postoperative clinical data were analysed. Post-pneumonectomy ALI / ARDS developed within the first postoperative week in 18 (12%) patients. Patients who developed ALI / ARDS had a longer hospital duration of stay (median [interquartile range], 26 [18 to 75] vs. 8 [7 to 11] days; P < 0.001) and higher in-hospital mortality (12 [67%] vs. 0 [0%]; P < 0.001). In an univariate analysis, post-pneumonectomy ALI / ARDS was associated with larger tidal volume (V(T)) and higher airway pressure (P(aw)) during one-lung ventilation (V(T) 8.2 [7.5 to 9.0] vs. 7.7 [6.9 to 8.2] ml/kg predicted body weight, P = 0.016; P(aw), 28.9 [27.6 to 30.0] vs. 27.2 [25.6 to 28.5] cmH2O, P = 0.001). V(T) during two-lung ventilation was also greater in patients who developed ALI / ARDS (P = 0.014) than in those who did not, but P(aw) during two-lung ventilation did not differ (P = 0.950). In a multiple logistic regression analysis, post-pneumonectomy ALI / ARDS was independently associated with a larger V(T) (OR 3.37 per 1 ml/kg predicted body weight increase; 95% confidence interval 1.65 to 6.86) and higher P(aw) (OR 2.32 per 1 cmH2O increase; 95% confidence interval 1.46 to 3.67) during the period of one-lung ventilation. In conclusion, a large V(T) and high P(aw) during one-lung ventilation were associated with an increased risk of post-pneumonectomy ALI / ARDS in primary lung cancer patients.