To explore whether the variation of left ventricular outflow tract velocity time integral (LVOT VTI) between positive end-expiratory pressure (PEEP) 10 cmH2O and PEEP 0 cmH2O can predict fluid responsiveness in mechanically ventilated critically ill patients. An observational study. A tertiary hospital intensive care unit. A total of 79 critically ill patients who were on controlled mechanical ventilation. Transthoracic echocardiography was performed at different PEEP levels and was also performed before and after passive leg raising (PLR). The patients were classified as the fluid responders (n=45) and the fluid nonresponders (n=34) according to the LVOT VTI change after PLR (ΔVTIPLR). The difference of LVOT VTI between PEEP 10 cmH2O and PEEP 0 cmH2O (ΔVTIPEEP) was much higher in responders than in nonresponders (17.9% v 2.1%, p < 0.001). The ΔVTIPEEP and ΔVTIPLR were correlated among all patients (r=0.582, p < 0.001). The receiver operating characteristic curve analysis revealed that the ΔVTIPEEP was a good predictor of fluid responsiveness, with an area under the curve of 0.935 (95% confidence interval: 0.885-0.986, p < 0.001), and the optimal cutoff value was 10.5%. Variation of LVOT VTI between PEEP 10 cmH2O and PEEP 0 cmH2O can be used to predict fluid responsiveness in critically ill patients on controlled mechanical ventilation.