OBJECTIVE: The purpose of this study was to determine in vitro and in vivo the optimal threshold for renal lesion vascularity at low-energy (40-60 keV) virtual monoenergetic imaging. MATERIALS AND METHODS: A rod simulating unenhanced renal parenchymal attenuation (35 HU) was fitted with a syringe containing water. Three iodinated solutions (0.38, 0.57, and 0.76 mg I/mL) were inserted into another rod that simulated enhanced renal parenchyma (180 HU). Rods were inserted into cylindric phantoms of three different body sizes and scanned with single- and dual-energy MDCT. In addition, 102 patients (32 men, 70 women; mean age, 66.8 ± 12.9 [SD] years) with 112 renal lesions (67 nonvascular, 45 vascular) measuring 1.1-8.9 cm underwent single-energy unenhanced and contrast-enhanced dual-energy CT. Optimal threshold attenuation values that differentiated vascular from nonvascular lesions at 40-60 keV were determined. RESULTS: Mean optimal threshold values were 30.2 ± 3.6 (standard error), 20.9 ± 1.3, and 16.1 ± 1.0 HU in the phantom, and 35.9 ± 3.6, 25.4 ± 1.8, and 17.8 ± 1.8 HU in the patients at 40, 50, and 60 keV. Sensitivity and specificity for the thresholds did not change significantly between low-energy and 70-keV virtual monoenergetic imaging (sensitivity, 87-98%; specificity, 90-91%). The AUC from 40 to 70 keV was 0.96 (95% CI, 0.93-0.99) to 0.98 (95% CI, 0.95-1.00). CONCLUSION: Low-energy virtual monoenergetic imaging at energy-specific optimized attenuation thresholds can be used for reliable characterization of renal lesions.