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Hepatitis B virus is an ample cause of end-stage liver diseases and hepatocellular carcinoma. Effective treatment in high-risk countries such as Pakistan can help delay or prevent these consequences. The existing study aims to evaluate the response rates of antiviral drugs tenofovir and entecavir (6-48 months) based on different clinical parameters. Sera collected from HBV patients (43) subjected to DNA extraction, followed by real-time PCR detection. Furthermore, ICT was performed to detect HBs-Ag and ELISA for HBe-Ag. Response rate after 6 months of tenofovir treatments showed 100% normal creatinine and ultrasound and ALT (50%) and while in the case of entecavir, each ALT and ultrasound normalization (66.7%), showed creatinine (100%). The fatty liver was reported 50% and 33.3% after tenofovir and entecavir treatment, respectively. The response after 12 months of treatment with tenofovir showed normalization of ALT and ultrasound (84.6%), bilirubin and creatinine normalization (92.3%), and fatty liver (15.4%). Whereas bilirubin and creatinine levels showed (100%) normal, ALT and ultrasound normalization (80%) with 20% of patients having congenital left lobe of the liver after entecavir. Patients profiles after 24 months of tenofovir treatment showed normal ALT and ultrasound (85.7%), bilirubin (100%), and renal impairment observed in patients (14.3%). The 24 months entecavir treatment showed significant improvement in various clinical parameters normalization with 100% such as ALT, bilirubin, and creatinine in all patients. The efficacy of entecavir showed a significant response as compared to Tenofovir. Furthermore …