The incidence and mortality in pregnant women with acute liver failure caused by hepatitis E virus (HEV) is high. Data on the viral load of HEV during pregnancy are limited. The study was designed to determine the viral load of HEV and its association with the disease severity in patients with acute liver failure. A total of HEV related 163 patients with acute liver failure which included 105 pregnant, 46 non-pregnant women and girls and 12 men and 730 patients with acute viral hepatitis which comprised of 220 pregnant women; 282 non-pregnant women and girls and 228 men were included. Viral load was measured by real-time PCR. Comparison was made between the pregnant and non-pregnant women. HEV RNA was detectable in 265 patients (142 pregnant; 75 non-pregnant and 48 men) and 104 patients with acute liver failure (64 pregnant, 34 non-pregnant and 6 men). The viral load of HEV in pregnant women with acute liver failure and acute viral hepatitis was significantly higher 129,984.0 ± 103,104.17 and 768.92 ± 1,105.40 copies/ml, respectively compared to the non-pregnant women which was 189.2 ± 225 and 12.73 ± 7.8 copies/ml (P < 0.0001). The viral load of HEV was also significantly higher in the pregnant patients with acute liver failure compared to the pregnant women with acute viral hepatitis and also men (P < 0.0001). High viral load of HEV during pregnancy could be one of the factors responsible for the severity of the infection during pregnancy. J. Med. Virol. 85:620–626, 2013. © 2012 Wiley Periodicals, Inc.