The study evaluated the efficacy and safety of tenofovir amibufenamide (TMF) in 186 patients with chronic hepatitis B, with 93 receiving TMF and 93 tenofovir disoproxil (TDF) for 48 weeks. Virologic response rates were not significantly different between groups (p > 0.05). Normalization of serum alanine aminotransferase (ALT) was significantly higher in the TMF group (76.34% vs. 60.22% in the TDF group, p < 0.05). The HBeAg seroconversion rate was higher with TMF (22.78% vs. 9.21%, p < 0.05). Serum creatinine levels were lower in the TMF group after 48 weeks (77.36 ± 16.87 μmol/L vs. 90.12 ± 17.23 μmol/L, p < 0.05). There were no significant differences in uric acid, calcium or phosphate levels. TMF is an effective treatment for chronic hepatitis B with better ALT normalization, higher HBeAg seroconversion and more favorable renal safety compared to TDF.