We designed this study to determine the predictive value for fluid responsiveness of stroke volume variation (SVV) in patients undergoing one-lung ventilation (OLV), ventilated at different tidal volumes. All patients scheduled for pulmonary lobectomy were randomized into two groups according to their tidal volume [group H: tidal volume 8 ml/kg (n = 36); group L: tidal volume 6 ml/kg (n = 37)]. After starting OLV, volume loading was performed by administration of 500 ml 6% hydroxyethylated starch for 30 min. Hemodynamic variables were measured before and after volume loading using the Vigileo-FloTrac system. Patients in both groups were divided into fluid responders and non-responders, and responders were defined as those who demonstrated an increase in cardiac index ≥15% after volume expansion. The area under the receiver operating characteristic curve for SVV to discriminate between responders and non-responders was 0.776 in group H and 0.648 in group L. The optimal threshold value of SVV was 10.5% (sensitivity, 85.7%; specificity, 66.7%) in group H and 8% (sensitivity, 69.5%; specificity, 64.3%) in group L. We found that SVV could predict fluid responsiveness in patients undergoing OLV with acceptable levels of sensitivity and specificity only when tidal volume is at least 8 ml/kg.