Aim of the study was to test individual mechanical and functional responses to open chest lateral decubitus during one lung ventilation. We measured dependent lung pressure volume (P-V) curves of 19 patients during supine and lateral decubitus. We found that patients characterized by high FEV1 developed greater changes in P-V curve shape than those characterized by low FEV1. Based on these results we decided to test a ventilation strategy characterized by the use of ZEEP or PEEP = 10 cm H2O applied to the dependent lung. In a preliminary set of patients stratified by FEV1 we found that PEEP deteriorated PaO2/FiO2 in patients with low FEV1, while there was a trend towards improvement in patients with high FEV1. It is possible that dependent lung PEEP counteracts atelectasias in normal lungs, while it may divert blood flow or create dead space in patients with sick and stiff lungs. We conclude that during one lung ventilation in open chest lateral decubitus, ventilatory setting need to be individually tailored.