PURPOSE: To determine whether dual-energy multidetector CT enables detection of renal lesion enhancement by using calculated nonenhanced images with spectral-based extraction in a non-body weight-restricted patient population. MATERIALS AND METHODS: Between January 2008 and December 2009, 139 patients were enrolled in this prospective HIPAA-compliant, institutional review board-approved study. Written informed consent was obtained from all patients. After single-energy nonenhanced 120-kVp CT images were acquired, contrast material-enhanced dual-energy multidetector CT images were acquired at 80 and 140 kVp. Calculated nonenhanced images were generated by using spectral-based iodine extraction. Lesion attenuation was measured on the acquired nonenhanced, calculated nonenhanced, and 140-kVp contrast-enhanced nephrographic images. Enhancement, defined as a 15-HU or greater increase in attenuation on the nephrographic images, was assessed by using the baseline attenuation on the acquired and calculated nonenhanced images. Acquired nonenhanced versus calculated nonenhanced image attenuation, as well as enhancement values, were compared by using paired Student t tests and Bland-Altman plots. RESULTS: Hypoattenuating (n = 66) and hyperattenuating (n = 28) cysts, angiomyolipomas (n = 18), and solid enhancing lesions (n = 27) were detected. Mean attenuation values for hypoattenuating cysts on the acquired and calculated nonenhanced CT images were 6.5 HU ± 5.8 (standard deviation) and 8.1 HU ± 3.1 (P = .13), respectively, with corresponding enhancement values of 1.1 HU ± 5.2 and -0.5 HU ± 6.2 (P = .12), respectively. Mean values for hyperattenuating cysts were 29.4 HU ± 5.6 on acquired images and 31.7 HU ± 5.1 on calculated images (P = .39) (corresponding enhancement, 4.7 HU ± 3.3 and 2.3 HU ± 4.1, respectively; P = .09). Mean values for fat-containing enhancing lesions were -90.6 HU ± 24.7 on acquired images and -85.9 HU ± 23.7 on calculated images (P = .57) (corresponding enhancement, 18.2 HU ± 10.1 and 13.6 HU ± 10.7, respectively; P = .19). Mean attenuation values for solid enhancing lesions were 26.0 HU ± 15.0 on acquired images and 27.7 HU ± 14.9 on calculated images (P = .45) (corresponding enhancement, 60.3 HU ± 13.1 and 58.3 HU ± 15.5, respectively; P = .38). CONCLUSION: Dual-energy CT acquisitions with spectral-based postprocessing enabled accurate detection of renal lesion enhancement across the attenuation spectrum of frequently encountered renal lesions in a non-body habitus-restricted patient population.