BACKGROUND: Vietnam has one of the highest hepatitis B virus (HBV) infection rates, with approximately 8 million people affected. Although antiviral drug resistance mutations have been reported in treatment-naïve patients with chronic hepatitis B, there is limited data on primary drug resistance mutations in circulating genotypes within this population. OBJECTIVES: This study aimed to investigate primary antiviral drug resistance mutations and common HBV genotypes in treatment-naïve patients with chronic hepatitis B, particularly in cases without well-characterized resistance profiles. DESIGN: A cross-sectional study. METHODS: We analyzed HBV genotypes and antiviral drug resistance mutations in 113 treatment-naïve patients with chronic hepatitis B in the Yenphong Medical Center, Bacninh Vietnam. The reverse transcriptase (RT) region of the HBV polymerase genes was sequenced to detect mutations. RESULTS: Genotypes B, C, and G were identified in 85.0% (96/133), 14.1% (16/133), and 0.9% (1/133) of treatment-naïve patients with chronic hepatitis B, respectively. Mutations in the RT region associated with antiviral drug resistance were detected in 32.7% (37/113) of patients. In addition, the most frequent resistance mutations were rtV207M (89.2%, 33/37), followed by A194T, L180M + M204V, V173L + M204I + L80I, and A181T + V207M + A181T, each observed in 2.7% (1/37). Notably, no significant associations were found between resistance mutations and HBV genotype, gender, age, hepatitis B e-antigen status, baseline HBV DNA levels, or level of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase. CONCLUSION: This study highlights the presence of primary resistance mutations in treatment-naïve patients and underscores the importance of genotypic screening prior to initiating therapy. These findings may inform treatment strategies and help reduce the risk of treatment failure, liver cirrhosis, and hepatocellular carcinoma.