OBJECTIVE To assess the diagnostic performance of follow-up liver computed tomography (CT) for the detection of high-risk esophageal varices in patients treated with locoregional therapy for hepatocellular carcinoma (HCC). METHODS We prospectively enrolled 100 patients with cirrhosis who underwent transcatheter arterial chemoembolization, radiofrequency ablation or both procedures for HCCs. All patients underwent upper endoscopy and subsequently liver CT. Three radiologists independently evaluated the presence of high-risk esophageal varices with transverse images alone and with three orthogonal multiplanar reformation (MPR) images, respectively. With endoscopic grading as the reference standard, diagnostic performance was assessed by using receiver operating characteristic (ROC) curve analysis. RESULTS The diagnostic performances (areas under the ROC curve) of three observers with transverse images alone were 0.947 ± 0.031, 0.969 ± 0.024, and 0.916 ± 0.038, respectively. The mean sensitivity, specificity, positive predicative value (PPV), and negative predicative value (NPV) with transverse images alone were 90.1%, 86.39%, 70.9%, and 95.9%, respectively. The diagnostic performances, mean sensitivity, specificity, PPV, and NPV with three orthogonal MPR images (0.965 ± 0.025, 0.959 ± 0.027, 0.938 ± 0.033, 91.4%, 89.5%, 76.3%, and 96.6%, respectively) were not superior to corresponding values with transverse images alone (P > 0.05), except for the mean specificity (P = 0.039). CONCLUSIONS Our results showed excellent diagnostic performance, sensitivity and NPV to detect high-risk esophageal varices on follow-up liver CT after locoregional therapy for HCC.