Abstract: OBJECTIVE To study the effect of viral load of telbivudine and entecavir on chronic hepatitis B with HBeAg positive, so as to make the treatment plan of alternate use two medicines. METHODS A total of 200 patients with HBeAg positive chronic hepatitis B from Jun. 2012 to Jun. 2014 in our hospital were divided into the telbivudine group(102 cases)and entecavir group(98 cases)according to the treatment methods, and the two groups were treated for 24 weeks. The level of serum alanine aminotransferase (ALT), HBeAg and hepatitis B virus E antibody (anti-HBe) were detected, and the ALT normalization rate, HBeAg disappear rate and HBeAg/anti-HBe conversion rate were calculated. The HBV DNA ration of two groups of patients before and after the treatment was tested by real-time fluorescent quantitative PCR method. In addition, using univariate and multivariate to analyze clinical efficacy of 12 weeks and 24 weeks of viral load. RESULTS After 24 weeks of treatment, serum ALT recovery rate differences were not significant; serum HBeAg disappearance rate and HBeAg/anti HBE conversion rates of the telbivudine group were significantly higher than the entecavir group (P<0.05). Single factor analysis showed that treatment for 12 weeks and 24 weeks, HBV DNA was the influence factor to effect telbivudine on HBeAg positive chronic hepatitis B(P<0.05), and treatment for 24 weeks, HBV-DNA was entecavir treatment factors affecting the efficacy of HBeAg positive chronic hepatitis B (P<0.05). CONCLUSION The treatment of 12 weeks of viral load has influence on telbivudine treatment, and 24 weeks of treatment has influence on viral load on entecavir and telbivudine treatment. Viral load should be timely detected in clinic in order to ensure the clinical curative effect of drugs, and reasonably use in an alternate way.