A molecular epidemiological survey of various hepatitis viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV), was carried out in Ho Chi Minh City, Vietnam. This study included of 295 patients with liver disease (234 viral related and 61 non-viral related) and 100 healthy individuals. The infection rates of HBV and HCV in 234 liver disease patients with acute hepatitis, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, were 31.2 and 19.2%, respectively. On the other hand, detection rates of these viruses in healthy populations were 10 and 2%, respectively (P<0.005 and <0.0001, respectively). None of cases tested was positive for HDV RNA. The most common viral genotypes were type B and C of HBV (43 and 57%) and type 2a of HCV (33.3%). Surprisingly, high prevalence of HBV pre-S2 deletion mutant was found in 22 of 87 (25.3%) patients with chronic liver disease. Moreover, antibody to hepatitis E virus (HEV) immunoglobulin G (IgG) was detected in 78 of 185 (42%) and IgM in 1 of 185 (0.5%) patients. The age prevalence of anti-HEV IgG was reached 61.9% in 21-40-year-olds. These results suggest that these hepatitis viruses, except for HDV, are spreading among liver disease patients in Ho Chi Minh city, Vietnam and HBV was the most important causative agent correlated with liver disease in this area.