Hepatitis D virus (HDV) is a defectivevirus thatrequires the presence of hepatitis B virus (HBV) for infection. It has been estimated that approximately 5% of the global hepatitis B surface antigen (HBsAg) carriers are also co-infected with HDV, leading to a total of 10-15 million HDV carriers worldwide. In the current study, we investigated anti-HDV seroprevalance, epidemiological features and effect of HDV on HBV morbidity and presence ofHBe antigen markers among 216 HBsAg seropositive patients recruited from four hospitals in Egypt between October 2009 and October 2011. Anti-HDV assay was performed by enzyme immunoassay (EIA). Then, the HDV seropositive patients were further investigated for HBe antigen and antibody, HBV DNA and HBV genotyping.Out of 216 HBsAg positive patients, 32 (14.8%) were anti-HDV positive. This study confirmed a declining trend in the prevalence of HDV infection in Egypt. A suppressive effect of HDV on HBV replication was suggested from the lower rate of detection of HBeAg (3.13%), which is indirectly proportional to viral replication, and the higher rate of detection of HBeAb (75%) in anti-HDV positive patients.