Hepatitis D virus (HDV) infection, also known as delta virus, has been identified as a crucial risk factor contributing to severe complications among hepatitis B patients. Such complications arise as HDV accelerates the progression towards cirrhosis, exacerbates the risk of decompensated cirrhosis, and increases mortality rates compared to non-HDV hepatitis B infections. Despite its clinical significance, data on HDV infection remains scarce, and exhibits marked regional disparities in Viet Nam. This study endeavors to explore HDV co-infection in adult hepatitis B patients. A descriptive cross-sectional investigation was conducted, involving 539 hepatitis B subjects attending the Outpatient Clinic of the Pasteur Institute in Ho Chi Minh City between October 2021 and May 5, 2022. The study sample featured three hepatocellular carcinoma (HCC) patients, 148 patients with elevated alanine aminotransferase (ALT) levels, and nine patients whose ALT levels exceeded five times the upper limit of normal (ULN). Additionally, 11 patients reported a history of blood transfusion, while no participants had any history of intravenous drug use. Remarkably, the study did not document any instances of HDV co-infection among the subjects. These findings suggest that HDV screening may not be a routine recommendation for patients diagnosed with moderate or mild hepatitis B, particularly when presenting with low-risk factors. Further research is warranted to better understand the prevalence of HDV co-infection in this population and to guide the development of evidence-based screening guidelines.