INTRODUCTION: The aims of the present study were to assess the rates of hepatitis B virus (HBV) reactivation and to identify the predictors of relapse in CHB who discontinued entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy. METHODS: Between January 2015 and January 2017,36 non-cirrhotic chronic hepatitis B (CHB) patients who had received TDF or ETV for ≥ 5 years (serum HBV DNA negative for ≥ 2 years, a liver stiffness 2 × upper limit of normal and HBV DNA ≥20.000 IU/mL in two consecutive measurements that were at least 1 months apart after stopping NAs therapy. The median off treatment follow up duration was 26 months. RESULTS: NAs treatment was discontinued in 36 patients(median age:53 years;25 males/11 females). At the treatment cessation, 32 patients had TDF and 4 patients had ETV therapy. CHB patients had been treated with NAs for a median duration of 77 months. Twenty-six patients had previously received other anti-HBV treatments for CHB, while 10 patients had no treatment. During the follow-up period, no patient died, developed jaundice or liver decompensation due to HBV reactivation. Relapse was occurred in 9 patients;6 of them had relapsed in the first 6 months. The cumulative relapse rates were 2,8% at 3 months, 16,7% at 6 months, 22,1% at 12 months and 26,1% at 24 months, respectively. No significant differences in terms of HBV reactivation including age, gender, the duration of NA treatment, type of antiviral therapy, baseline serum ALT and HBVDNA levels, histological activity index and a liver stiffness and at the end of treatment quantitative HBsAg levels among patients with/without HBV reactivation. HBsAg quantitative values decrease in all patients. The ratio of CHB patients with HBsAg