Background: Chronic hepatitis B virus infection is an important cause of morbidity and mortality. Tenofovir disoproxil fumarate was licensed for the treatment of hepatitis B virus infection. So, the current study aimed to Evaluate efficacy and outcome of Tenofovir Disoproxil Fumarate in patients with Chronic Hepatitis B with High Baseline Viral Load. Patients and methods:One hundred Chronic HBV patients attend Outpatient Clinic of HBV treatment unit, Qena fever hospital, Qena, Egyptwere enrolled in this study and treated with Tenofovir Disoproxil Fumarate (300mg/day) for 24 weeks. Patients categorized into two groups: Group A: included 50 chronic HBV patients with Low Viral load < 1 million/ml and Group B: included 50 chronic HBV patients with High Viral load ≥ 1 million/ml.virological and biochemical response, as well as safety outcomes were assessed after 24 weeks of treatment. Results:The mean age of patients was 38.4 years and 33.9 years in Group A and Group B respectively. Number of males was 32 (64%) and 36 (72%) in Group A and Group B respectively. HBeAg was positive in 20 % and 36 % in Group A and Group B respectively. The rates of complete virological suppression were 88% in group A and 72% in group B. All patients achevied normalization of ALT. No severe adverse events were reported during the present study. No elevations in creatinine level were detected. Conclusion: Tenofovir Disoproxil Fumarate is an efficacious, safe and well-tolerated treatment in an Egyptian patient.