Background This study aimed to investigate changes in the hepatic venous pressure gradient (HVPG) by partial splenic embolization (PSE) and to identify the determinants of a clinically meaningful postoperative HVPG reduction. Methods Sixty-eight patients with cirrhosis and hypersplenism who underwent PSE at our department between September 2007 and June 2020 were included. The HVPG was evaluated pre- and immediately post-PSE. The patients were divided into three groups according to their preprocedural HVPG: low-HVPG (< 10 mmHg, n = 22), intermediate-HVPG (10 mmHg <= HVPG < 16 mmHg, n = 33), and high-HVPG (>= 16 mmHg, n = 13). Results Overall, PSE significantly reduced HVPG from 12.2 +/- 4.0 to 9.4 +/- 3.6 mmHg (p < 0.01) with a relative decrease of 22.2 +/- 20.4%. In addition, HVPG reductions were 19.4 +/- 28.7%, 24.0 +/- 15.9%, and 22.5 +/- 13.3% in the low-, intermediate-, and high-HVPG groups, respectively, indicating no significant difference in HVPG reduction between the groups. An HVPG decrease of >= 20% from the baseline, defined in this study as a clinically significant HVPG response to PSE, was achieved in 55.9% of all patients. Multivariate logistic regression and receiver operating characteristic curve analyses identified splenic non-infarction volume as an independent determinant of a 20% decrease in HVPG (p < 0.05), with a cut-off of 139.2 cm(3) (sensitivity, 76.3%; specificity, 60.0%; p < 0.05). Conclusions The splenic non-infarction volume, namely the residual functional spleen volume, independently determines a clinically significant HVPG response to PSE in patients with cirrhosis and hypersplenism.