Summary This study investigates the incidences and predictors of hepatitis B virus (HBV) relapse after tenofovir disoproxil fumarate (TDF) therapy in hepatitis B e antigen (HBeAg)‐positive and ‐negative patients. We retrospectively recruited 143 chronic hepatitis B (CHB) patients without cirrhosis (39 HBeAg‐positive and 104 HBeAg‐negative patients) who were previously treated with TDF and had post‐treatment follow‐up for at least 6 months (median: 55, IQR 36‐85 weeks). All the patients fulfilled the stopping criteria of APASL 2012. The virological and clinical relapse rates at 104 weeks in HBeAg‐positive patients were 66.6% and 59.1%, while they were 72.3% and 55.9%, respectively, in HBeAg‐negative patients. Cox regression analysis revealed that the higher end‐of‐treatment HBsAg levels were an independent factor of virological relapse in HBeAg‐positive and HBeAg‐negative patients. The end‐of‐treatment HBsAg levels of 200 (area under the receiver operating characteristic (AUROC): 0.624) and 80 IU/mL (AUROC: 0.959) were the optimal values for predicting HBV relapse in HBeAg‐positive and HBeAg‐negative patients, respectively. The virological relapse rate at 78 weeks was 14.3% and 19.6% in HBeAg‐positive and HBeAg‐negative patients who achieved HBsAg ≤200 IU/mL and HBsAg ≤80 IU/mL, respectively. Two patients experienced hepatic decompensation upon hepatitis flares, and no patient died after timely retreatment. Seven patients experienced off‐therapy HBsAg loss. The cumulative rates of HBsAg loss at 104 weeks were 45.5% and 59.3% in patients with end‐of‐treatment HBsAg ≤80 IU/mL and ≤50 IU/mL, respectively. In conclusions, the end‐of‐treatment HBsAg levels were a useful marker for predicting HBV relapse in HBeAg‐positive and HBeAg‐negative CHB patients.