Purpose To determine whether contrast material-enhanced dual-energy multidetector computed tomography (CT) with material decomposition analysis allows differentiation of adrenal adenomas from nonadenomatous lesions and to compare findings with those of nonenhanced multidetectorCT. Materials and Methods This retrospective HIPAA-compliant study was approved by the institutional review board of Duke University, with waiver of informed consent. Thirty-eight nonconsecutive patients (22 men and 16 women; mean age, 65 years) with 47 adrenal nodules underwent nonenhanced and contrast-enhanced dual-energy multidetector CT of the abdomen. For each adrenal nodule, nonenhanced attenuation values were recorded; dual-energy density measurements were obtained by using fat-iodine and fat-water material density basis pairs. Mean and median values of nonenhanced attenuation and material densities were compared between adenomas and nonadenomas by using the two-sample t test and Wilcoxon rank sum test, respectively. The diagnostic performance of nonenhanced multidetector CT and dual-energy material densities was assessed by setting the specificity for diagnosis of adenomas at 100%. Results Adenomas (lipid rich and lipid poor) displayed significantly different mean density values (in milligrams per cubic centimeter) than those of nonadenomas on fat-iodine (970.4 ± 17.2 vs 1012.3 ± 9.3), iodine-fat (2.5 ± 0.3 vs 4.5 ± 1.5), fat-water (-666.7 ± 154.8 vs -2141.8 ± 953.2), and water-fat (1628.4 ± 177.3 vs 3225 ± 986.1) images, respectively (P < .0001). For diagnosis of adenomas, dual-energy material density analysis showed a sensitivity of 96% (23 of 24 lesions) at a specificity of 100% (23 of 23 lesions), yielding significantly improved diagnostic performance compared with nonenhanced multidetector CT attenuation (sensitivity of 67% [16 of 24 lesions] at a specificity of 100% [23 of 23 lesions]) (P = .035). Conclusion Contrast-enhanced dual-energy multidetector CT with material density analysis allows differentiation between adrenal adenomas and nonadenomas, reflecting an improved ability over nonenhanced multidetector CT for diagnosis of lipid-poor adenoma. © RSNA, 2014.