Background: When applying lung-protective ventilation, fluid responsiveness cannot be predicted by pulse pressure variation (PPV) or stroke volume variation (SVV). Functional hemodynamic testing may help address this limitation. This study examined whether changes in dynamic indices such as PPV and SVV, induced by tidal volume challenge (TVC), can reliably predict fluid responsiveness in patients undergoing renal transplantation who receive lung-protective ventilation. Methods: This nonrandomized interventional study included renal transplant recipients with end-stage renal disease. Patients received ventilation with a 6 mL/kg tidal volume (TV), and the FloTrac system was attached for continuous hemodynamic monitoring. Participants were classified as responders or nonresponders based on whether fluid challenge increased the stroke volume index by more than 10%. Results: The analysis included 36 patients, of whom 19 (52.8%) were responders and 17 (47.2%) were nonresponders. Among responders, the mean ∆PPV 6-8 (calculated as PPV at a TV of 8 mL/kg predicted body weight [PBW] minus that at 6 mL/kg PBW) was 3.32±0.75 and ∆SVV 6-8 was 2.58±0.77, compared to 0.82±0.53 and 0.70±0.92 for nonresponders, respectively. ∆PPV 6-8 exhibited an area under the curve (AUC) of 0.97 95% confidence interval [CI], 0.93–1.00; P≤0.001), with an optimal cutoff value of 1.5, sensitivity of 94.7%, and specificity of 94.1%. ∆SVV 6-8 displayed an AUC of 0.93 (95% CI, 0.84–1.00; P≤0.001) at the same cutoff value of 1.5, with a sensitivity of 94.7% and a specificity of 76.5%. Conclusions TVC-induced changes in PPV and SVV are predictive of fluid responsiveness in renal transplant recipients who receive intraoperative lung-protective ventilation.