Background/aims: Chronic hepatitis B virus infection is an important cause of morbidity and mortality. Tenofovir disoproxil fumarate and entecavir were licensed for the treatment of hepatitis B virus infection. We evaluated the first 12 months of chronic hepatitis B treatments with tenofovir and entecavir and compared their efficiencies. Methods: The study enrolled 94 chronic hepatitis B patients with compensated liver disease. The entecavir group consisted of 29 patients who received entecavir 0.5 mg/day and the tenofovir group consisted of 65 patients who received tenofovir 245 mg/day. There was no statistically significant demographic or HBeAg status difference between the groups. Patients returned to the clinic every four weeks for laboratory assessments of serum chemical and hematologic values, liver function and for documentation of any adverse events. Hepatitis B serologic markers and HBV-DNA levels were assessed every 12 weeks. The primary efficacy endpoint was a plasma HBV-DNA level of less than 400 copies es/ml over 48 weeks. Results: At the end of 48 weeks, treatment with either tenofovir or entecavir resulted in clinically important suppression of HBV-DNA, as 71.3%. There was no statistical difference in inducing undetectable levels of HBV-DNA between the entecavir (69%) and tenofovir (72.3%) groups. Furthermore, no side effect as an increase in creatinine was seen. HBeAg seroconversion was seen in only one patient in the entecavir group, but in no patients of the tenofovir group. Conclusions: In the first year of treatment for chronic hepatitis B, virologic response and tolerability did not differ significantly between tenofovir and entecavir. Both drugs are safe and efficacious for patients infected with HBV.