Background and Aim: We measured liver stiffness (LS) in patients with acute liver disease (ALD) using Virtual touch quantification (VTQ) and investigated the usefulness of measuring LS for predicting the prognosis of ALD patients. Materials and Methods: From April 2010 to December 2012, we evaluated 51 patients with ALD. The subjects included 32 patients with acute hepatitis (AH), 14 patients with acute hepatitis severe form (AH-s), who had no hepatic encephalopathy despite plasma prothrombin time of <40%, and five patients with fulminant hepatitis (FH) diagnosed according to the criteria of the Japanese Study Group. The relationships among velocity of shear wave (Vs), clinical diagnosis, liver function tests, and prognosis were evaluated. Receiver operating characteristic (ROC) analysis was performed to investigate whether VTQ exhibits potential usefulness for the early prediction of FH. In addition, we investigated the relationship between LS and the grade of liver damage using D-galactosamine-induced acute hepatitis in rats. Results: Vs on admission was 2.03 ± 0.55 m/s, 2.54 ± 0.56 m/s, and 3.65 ± 0.86 m/s in the AH, AH-s, and FH groups, respectively. Vs was significantly higher in the FH group than in the other groups (p<0.001). The area under the ROC curve for predicting FH was 0.893 (sensitivity 80.0, specificity 93.5). Vs was significantly increased in the non-survivors (n=4), while it decreased in survivors (n=47) (p=0.003). Vs by grade of liver damage was G0: 1.07 ± 0.05 m/s, G1: 1.27 ± 0.09 m/s, G2: 1.54 ± 0.23 m/s, and G3: 1.99 ± 0.16 m/s. Vs increased significantly with the severity of hepatic inflammation and necrosis (p<0.01). Conclusion: Vs measured by VTQ reflects the severity of liver damage, and the serial changes in Vs predict the prognosis of ALD patients. Vs is an early and precise biomarker of FH.