OBJECTIVE To determine whether intravenous propofol-alfentanil anesthesia provides superior arterial oxygenation (Pao2) during one-lung ventilation (OLV) compared with isoflurane inhalation anesthesia. METHODS A prospective, randomized, cross-over study. METHODS Tertiary-care university hospital. METHODS Thirty adults having either thoracoscopic pulmonary surgery or esophageal surgery. METHODS Patients received either propofol-alfentanil infusion anesthesia or one minimum alveolar concentration (MAC) of isoflurane during the initial period of two-lung ventilation and the first 30 minutes of OLV and then were switched to the other anesthetic for the duration of OLV. RESULTS Arterial blood gases and hemodynamics were recorded during two-lung ventilation and after 20 and 30 minutes of OLV with each anesthetic technique. The mean values (+/- SD) for Pao2 during propofol-alfentanil anesthesia after 20 minutes (222 +/- 100) and 30 minutes (228 +/- 102 mmHg) of one-lung ventilation were not significantly different than after 20 minutes (213 +/- 99) or 30 minutes (214 +/- 96 mmHg) of isoflurane; beta error less than 0.1. Mean heart rate was lower during intravenous (78 +/- 15 min) than inhalation (85 +/- 17 min) anesthesia (rho = 0.03). CONCLUSIONS This study does not support the theory that total intravenous anesthesia will decrease the risk of hypoxemia during OLV.