Background: Currently, pulse pressure variation (PPV) is considered the gold standard dynamic variable for predicting fluid responsiveness. Distensibility index of inferior vena cava (dIVC) is also considered a good predictor of fluid responsiveness. However, information from literature comparing the performance of both variables is still patchy and insufficient. Therefore, we aimed to investigate the accuracy of dIVC and PPV in predicting fluid responsiveness and compare the predictive power of both techniques. Methods: We conducted our study in shocked patients receiving mechanical ventilation requiring fluid challenge. Hemodynamic variables, such as PPV and dIVC, were recorded before and after fluid challenges. Fluid responders were identified when cardiac output increased more than 15% after the first fluid challenge. Only the non-responders received a second fluid challenge (SFC) to define delayed responders. Results: A total of 38 shocked patients were enrolled in this study. Twenty-one patients (55.3%) were fluid responders. The area under the receiver operating characteristic (AUROC) curve of PPV was 0.78 ^ 0.08 with a best cutoff of 10.5 (sensitivity: 76.2%; specificity: 70.6%). The AUROC curve of dIVC was 0.75 ^ 0.07, and the best cutoff value to predict fluid responsiveness was 16.5% with a sensitivity of 71.43% and specificity of 76.5%. Four patients from the non-responder group became responders after the SFC. No statistically significant difference was observed between the predictive performance of PPV and dIVC. Conclusions: Our findings indicate that the performance of PPV for predicting fluid responsiveness was similar to that of dIVC. PPV and dIVC are moderately predictive of fluid responsiveness.