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Objective: Interferon-alpha has been used in the treatment of chronic hepatitis B (CHB) for two decades. Diagnosis and treatment of CHB have improved in recent years with the introduction of new oral antiviral drugs. In this study, treatment results of patients with CHB followed for five years were evaluated. Methods: Between January 2004 and December 2009, 583 patients were treated in the Out-Patient Clinic of Infectious Diseases and Clinical Microbiology. Of these, 167 patients were included in the study. The remaining patients were excluded due to the short span of treatment (less than one year). Results: 27 (16%) of the patients were HBeAg-positive and 140 (84%) of them were HBeAg-negative. All of the patients were found to be of genotype D. The study group consisted of 40 (24%) patients who received only interferon and had not yet relapsed at least in one-year follow-up, 70 (42%) patients who used oral antiviral drugs due to relapses after completion of interferon therapy and 57 (34%) patients who used only oral antivirals due to contraindications for interferon treatment. Drug resistance to lamivudine was found in 18 of 55 (32%) patients and to adefovir in 4 of 53 (8%) patients. Lamivudine resistance was observed in only 2 of the patients, who received interferon before lamivudine therapy. We found that, of 27 (16%) HBeAg-positive patients, 4 showed anti-HBe seroconversion. Of the entire study group of 167 patients, 2 (1%) developed anti-HBs seroconversion. Conclusions: We conclude that chronic hepatitis B requires life-long follow-up and treatment and the treatment schedule should be individualized. When appropriate, the treatment should begin with interferon, and if necessary, proceed with the use of oral antivirals. We believe this regimen may help delay the development of antiviral resistance. [ABSTRACT FROM AUTHOR]