Background and Aims: We aimed to evaluate the effectiveness of nucleoside analogues such as Lamivudine, Adefovir, Entacavir, and Tenofovir in patients with chronic hepatitis B who failed to respond to interferon therapy and relapsed. Materials and Methods: We followed a total of 73 patients with hepatitis B in the hepatitis outpatient clinic in our hospital. The patients subsequently received nucleoside analogues therapy and their treatment data were evaluated retrospectively. The biochemical and virological response rates were evaluated at 3 and 12 months, and we compared these results with the results of treatment-naive patients.Results: There were 29 (39.7%) HbeAg-positive and 44 (60.3%) HbeAg-negative patients, and their mean age was 35.8 (±13.4) years. Of these patients, 33, 18, 13 and 9 received Entacavir, Tenofovir, Lamivudine, and Adefovir treatment, respectively. In HbeAg-negative patients, at 3 months the biochemical and virological response (early response) rates were observed to be 91% and 98%), and at 12 months the two rates were 93% and 73%, respectively. In HbeAg-positive patients, the biochemical and virological response rates at 3 months were 83% and 97%, and the rates at 12 months were 90% and 48%, respectively. Conclusions: In CHB therapy with treatment-resistent patients, nucleoside analogues may be preferable. There are disadvantages to nucleoside analogues, such as a risk of developing resistance during therapy, reduced HBeAg seroconversion compared to interferons, and the therapy’s ambiguous duration. In our study, in HbeAg-negative patients who received nucleoside analogues, a lower biochemical response rate was detected in patients with 1 year of Lamivudine therapy compared to other therapies. For HbeAg-positive patients, the virological response rate was higher in 1 year of Tenofovir therapy than with other therapies.