To determine the prognostic value of CT-based splenic volume measurement in patients with compensated chronic liver disease (cCLD) from chronic hepatitis B (CHB). A total of 584 patients having multiphasic liver CT scans between January and December 2011 were retrospectively reviewed. Spleen volume was measured using a semi-automated three-dimensional volumetric software program. Electronic medical records and national registry data were reviewed to determine the diagnosis of hepatocellular carcinoma (HCC), hepatic decompensation, or death. The cumulative incidence (CI) of the development of decompensation, HCC occurrence, and overall survival (OS) were estimated by the Kaplan-Meier method. The Cox proportional hazard regression model was used to evaluate prognostic factors. The optimal cutoff spleen volume to predict each outcome was obtained using a minimal p value approach method. After a median follow-up of 92 months, 114 patients developed HCC with a 7-year CI of 17.2%. A larger spleen volume was a significant predictor of HCC occurrence (HR = 2.13, p = 0.009). Decompensation occurred in 30 patients with a 7-year CI of 5.0%, and a larger spleen volume was also significantly associated with the development of decompensation (HR = 4.66, p = 0.005). Twenty-three patients died, and their estimated 7-year OS was 96.4%. A larger spleen volume also significantly affected OS (HR = 6.15, p = 0.007). The optimal cutoff spleen volume was set at 532 mL for HCC occurrence, 656.9 mL for the development of decompensation, and 741.1 mL for OS. A larger spleen volume was significantly associated with HCC occurrence, development of decompensation, and poor OS in patients with cCLD from CHB. • Spleen volume could be easily acquired from routine multiphasic liver CT scan using a semi-automated 3D volumetric software program with excellent inter-observer agreement. • A larger spleen volume was significantly associated with a higher rate of hepatocellular carcinoma occurrence, the development of decompensation, and poor overall survival in patients with compensated chronic liver disease from chronic hepatitis B.