Predicting the response of cardiac output to volume administration remains an ongoing clinical challenge. The objective of our study was to compare the ability to predict volume responsiveness of various functional measures of cardiac preload. These included pulse pressure variation (PPV), stroke volume variation (SVV), and the recently launched automated respiratory systolic variation test (RSVT) in patients after major surgery. In this prospective study, 24 mechanically ventilated patients after major surgery were enrolled. Three consecutive volume loading steps consisting of 300 ml 6% hydroxyethylstarch 130/0.4 were performed and cardiac index (CI) was assessed by transpulmonary thermodilution. Volume responsiveness was considered as positive if CI increased by >10%. In total 72 volume loading steps were analysed, of which 41 showed a positive volume response. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.70 for PPV, 0.72 for SVV and 0.77 for RSVT. Areas under the curves of all variables did not differ significantly from each other (P>0.05). Suggested cut-off values were 9.9% for SVV, 10.1% for PPV, and 19.7° for RSVT as calculated by the Youden Index. In predicting fluid responsiveness the new automated RSVT appears to be as accurate as established dynamic indicators of preload PPV and SVV in patients after major surgery. The automated RSVT is clinically easy to use and may be useful in guiding fluid therapy in ventilated patients.