Objective Nucleos(t)ide analogues(NAs)na?ve chronic hepatitis B(CHB)patients were given rescue combination therapy after drug resistance to lamivudine or adefovir.Evolution of HBV mutation patterns and its impact on antiviral effects were studied.Methods Total of 142 na?ve CHB patients treated with lamivudine were randomly divided into two groups when lamivudine resistance occurred.One group was added with adefovir,the other was switched to entecavir and adefovir.Seventy-two na?ve CHB patients treated with adefovir were randomly divided into two groups when adefovir resistance occurred.One group was added with lamivudine,the other was added with entecavir.HBV polymerase reverse transcriptase mutations associated with resistance were analyed before and after 48weeks of rescue therapy,respectively.Results The mutation patterns of M204V/I,M204V+L180M were predominantly found in CHB patients after lamivudine resistance.Meanwhile,the entecavir resistance mutation patterns were also detected.Therefore,patients with lamivudine resistance could develop more diverse drug resistance mutations if they were switched to entecavir and adefovir.The mutation patterns of rtA181 were predominantly found in CHB patients after adefovir resistance and rescure therapy with add-on entecavir was more effective than with add-on lamivudine Conclusions Resistance mutation analysis chould help to choose NAs,reduce resistance and ehance antiviral effects. Objective Nucleos (t) ide analogues (NAs) na? Ve chronic hepatitis B (CHB) patients were given rescue combination therapy after drug resistance to lamivudine or adefovir. Evolution of HBV mutation patterns and its impact on antiviral effects were studied. Methods Total of 142 na? Ve CHB patients treated with lamivudine were randomly divided into two groups when lamivudine resistance occurred. One group was added with adefovir, the other was switched to entecavir and adefovir. Seventy-two na? Ve CHB patients treated with adefovir were randomly divided into two groups when adefovir resistance was occurred. One group was added with lamivudine, the other was added with entecavir. HBV polymerase reverse transcriptase mutations associated with resistance were analyzed before and after 48 weeks of rescue therapy, respectively. Results The mutation patterns of M204V / I , M204V + L180M were predominantly found in CHB patients after lamivudine resistance. Meanwhile while the entecavir resistance mutation patterns were also detected Therefore, patients with lamivudine resistance could develop more diverse drug resistance mutations if they were switched to entecavir and adefovir. The mutation patterns of rtA181 were predominantly found in CHB patients after adefovir resistance and rescure therapy with add-on entecavir was more effective than with add-on lamivudine Conclusions Resistance mutation analysis chould help to choose NAs, reduce resistance and ehance antiviral effects.