To explore the potential of CT quantitative parameters in differentiating adrenal lipid-poor adenoma (LPA) from nodular hyperplasia and evaluate diagnostic performance. Patients with LPA or nodular hyperplasia who underwent contrast-enhanced CT before adrenalectomy were analyzed retrospectively. The study included 128 patients (83 with LPA and 45 with nodular hyperplasia). Each lesion's unenhanced attenuation, portal-venous phase attenuation (CTp), and the portal-venous phase attenuation of the abdominal aorta were evaluated. We subsequently calculated absolute enhancement [a lesion's portal-venous phase attenuation minus unenhanced attenuation (in HUs)], relative enhancement (absolute enhancement divided by unenhanced attenuation), and the relative enhancement ratio [(absolute enhancement divided by abdominal aorta's portal-venous phase attenuation) ×100%]. Lesion number and size were recorded. Volume was assessed by ITK-snap software and the ratio of lesion volume to ipsilateral adrenal volume (volume ratio) was determined. Intergroup differences were analyzed using Student's t-test and chi-squared test. Logistic regression models were developed, and receiver operating characteristic (ROC) curves were constructed to determine the area under the ROC curve (AUC), sensitivity, and specificity. The model's performance was then compared against radiologists' subjective assessments, and the inter- and intra-reader agreement values among radiologists were calculated. Portal-venous phase attenuation, volume ratio, and lesion number were independent predictors of LPA. The logistic regression model incorporating CTp, volume ratio, and lesion number achieved an AUC of 0.835, with a sensitivity of 73.5% and a specificity of 80.0%. The radiologists' diagnostic specificity and accuracy appeared to be inferior to the model. The inter-reader agreement among radiologists ranged from 0.082 to 0.535, and the intra-reader agreement of two radiologists were 0.734 and 0.583. The portal-venous phase CT demonstrated potential in distinguishing LPA from nodular hyperplasia. The diagnostic performance of the model integrating CTp, volume ratio, and lesion number outperformed radiologists in terms of variability and reproducibility.