Background The value of CT in assessment of clinically significant portal hypertension (CSPH) has not been well determined. Purpose To evaluate the performance of CT features that have been associated with portal hypertension for diagnosing CSPH in patients with chronic liver disease (CLD). Materials and Methods This retrospective study included patients with CLD who underwent contrast-enhanced CT and subsequent hepatic venous pressure gradient (HVPG) measurement within 3 months at two tertiary institutions from January 2001 to December 2019. Two readers independently evaluated the presence of gastroesophageal varix, spontaneous portosystemic shunt (SPSS), and ascites on CT images. Splenomegaly at CT was determined using three methods, as follows: personalized or fixed volume criteria, based on spleen volume as measured by a deep learning algorithm, or manually measured spleen diameter. The diagnostic performance of these findings alone or in combination for detecting CSPH (HVPG ≥10 mm Hg) was evaluated. Results A total of 235 patients (mean age, 53.2 years ± 13.0 [SD]; 155 male patients), including 110 (46.8%) with CSPH, were included. Detection of CSPH according to the presence of both splenomegaly and at least one other CT feature (ie, gastroesophageal varix, SPSS, and ascites) achieved specificities of 94.4%-97.6%, whereas detection of CSPH according to the presence of any feature (ie, splenomegaly, gastroesophageal varix, SPSS, or ascites) achieved sensitivities of 94.5%-98.2%. When employing the former as rule-in criteria with the absence of splenomegaly, gastroesophageal varix, SPSS, and ascites as rule-out criteria for CSPH, 171-185 (range, 72.8%-78.7%) of 235 patients were correctly classified as either having CSPH or not, seven to 13 (range, 3%-5.5%) of 235 patients were incorrectly classified, and 42-54 (range, 17.9%-23%) of 235 patients were unclassified. Conclusion The presence or absence of splenomegaly, gastroesophageal varix, SPSS, and/or ascites on CT images may be useful for ruling in and ruling out CSPH in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Fraum in this issue.