Objective To observe  the effect of adefovir dipivoxil  initial  treatment and adefovir dipivoxil associated with  lamivudine  treantment after  lamivudine  resistance  in chronic hepatitis B  therapy. Methods Total of 45 patients were divided  into  two groups. Group A were  treated by  lamivudine associated with adefovir dipivoxil after lamivudine resistance. Group B were treated by adefovir dipivoxil as initial treatment. Liver function, kidney function and HBV DNA were detected before treatment and 12, 24, 36 and 48 weeks after treatment. Results After 12 and 24 weeks treatment, the rate of HBV DNA undetectable in group A was obviously higher  than  that  in group B, with statistical difference. After 48 weeks  treatment,  the quantitation and undetectable rate of HBV DNA, the normalization rate of ALT were not statistically significant. Normal kidney  function and no adverse effect were  found during  treatment  in  two groups. Conclusions Effect of chronic hepatitis B  therapy by adefovir dipivoxil  initial  treatment and  lamivudine associated with adefovir dipivoxil after lamivudine resistance were equally effective, which deserves continuative exploration.