To investigate if sevoflurane based anesthesia is superior to propofol in preventing lung inflammation and preventing postoperative pulmonary complications. Randomized controlled trial. Single tertiary care university hospital. Forty adults undergoing cardiac surgery with cardiopulmonary bypass. Patients were randomized in a 1:1 ratio to anesthetic maintenance with sevoflurane or propofol. Blood and bronchoalveolar lavage fluid was sampled before and after bypass to measure pulmonary inflammation using a biomarker panel. The change in bronchoalveolar lavage concentration of tumor necrosis factor alpha (TNFα) was the primary outcome. Secondary outcomes included lung inflammation defined as changes in other biomarkers and postoperative pulmonary complications. There were no significant differences between groups in the change in bronchoalveolar lavage TNFα concentration (median IQR change, 17.24 1.11-536.77 v 101.51 1.47-402.84 pg/mL, sevoflurane v propofol, p = 0.31). There was a significantly lower postbypass concentration of plasma interleukin 8 (median IQR, 53.92 34.5-55.91 v 66.92 53.03-94.44 pg/mL, p = 0.04) and a significantly smaller postbypass increase in the plasma receptor for advanced glycosylation end products (median IQR, 174.59 73.59-446.06 v 548.22 193.15-852.39 pg/mL, p = 0.03) in the sevoflurane group compared with propofol. The incidence of postoperative pulmonary complications was 100% in both groups, with high rates of pleural effusion (17/18 94.44% v 19/22 86.36%, p = 0.39) and hypoxemia (16/18 88.88% v 22/22 100%, p = 0.11). Sevoflurane anesthesia during cardiac surgery did not consistently prevent lung inflammation or prevent postoperative pulmonary complications compared to propofol. There were significantly lower levels of 2 plasma biomarkers specific for lung injury and inflammation in the sevoflurane group.