Some researches demonstrate that entecavir increases the incidence of virological and biochemical responses compared to lamivudine, although, they have shown inconsistent response rates. A metaanalysis was conducted to compare the efficacy of entecavir and lamivudine for chronic hepatitis B treatment. Two independent researchers identified pertinent clinical controlled trials. Our analysis includes nine case-control studies, which had 1251 entecavir groups and 1188 lamivudine groups. Analyses were performed with STATA version 9.0. Rates of virology and biochemical responses and HBeAg clearance and seroconversion were used as primary efficacy measures. Greater virological and biochemical responses rates were observed with entecavir to lamivudine after treatment of 48 weeks (odds ratio (OR) = 3.422, 95% confidence intervals (CI) = 2.349 -4.985, P = 0.000; OR = 2.173, 95% CI = 1.462 -3.230, P = 0.000, respectively), but no statistically significant differences were observed between cases and controls for clearance and seroconversion of HBeAg (P > 0.05). Safety and adverse-event profiles were similar in the two groups. In conclusion, this meta-analysis suggested that entecavir increases the incidence of virological and biochemical responses compared with lamivudine after treatment for 48 weeks.