Abstract Objective The purpose of this study was to assess the influence of liver cirrhosis and portal hypertension on diffusion coefficients of the spleen. Material and Methods We retrospectively evaluated 50 patients with liver cirrhosis and 50 patients without any history of liver disease who underwent magnetic resonance imaging of the upper abdomen, including echo planar diffusion-weighted imaging using b values of 50, 300 and 600mm2/s. Spleen apparent diffusion coefficient (ADC), liver ADC, muscle ADC and normalized spleen ADC (defined as the ratio of spleen ADC to muscle ADC) were compared between cirrhotic patients and patients in the control group and correlated with Child–Pugh stages. Reproducibility was assessed by measuring interclass correlation coefficient (n=11). Additionally, in eight patients, ADC measurements were performed 1 day before and 3 days after transjugular intrahepatic portosystemic shunt (TIPSS) implantation. Results Compared with control subjects, patients with cirrhosis and portal hypertension had significantly higher spleen ADCs (P=.0001). There was a statistically significant correlation between Child–Pugh grade and spleen ADC (Pearson correlation coefficient, observer 1 r=0.6, P=.0001; observer 2 r=0.5, P=.0001). After TIPSS implantation, we observed a reduction in spleen ADC values. Spleen ADC measurements showed a high reproducibility (interclass correlation coefficient 0.75, P=.001). Conclusion Our data suggest that different stages of liver cirrhosis and portal hypertension correlate with ADC values of the spleen. Furthermore, ADC values of the spleen decrease after TIPSS implantation. Further studies are required to understand the potential clinical values of these observations.