Summary Background/Aims To compare the rates of hepatitis B surface antigen (HBsAg) loss after discontinuation of entecavir versus tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) without cirrhosis. Methods A total of 891 patients who received entecavir (n = 556) or TDF (n = 335) followed up post‐treatment for at least 12 months were retrospectively assessed. A total of 677 patients who had continued entecavir or TDF therapy for at least 4 years were enrolled as the continued group. Results Patients who discontinued TDF had higher rates of virological and clinical relapse and retreatment than patients who discontinued entecavir in both the HBeAg‐positive and HBeAg‐negative subgroups. In the entire discontinued cohort, the cumulative rates of HBsAg loss at 7 years were 22.6% and 35.4% in the entecavir and TDF groups respectively. Patients who discontinued TDF had significantly higher rates of HBsAg loss than patients who discontinued entecavir therapy in all (p = 0.019) and propensity score‐matched (p = 0.015) patients, especially among the subgroups who achieved a sustained response (p < 0.001). Cox regression analysis revealed that TDF, longer treatment duration and lower HBsAg levels at end of treatment were independently associated with HBsAg loss in the entire discontinued group. The incidence of HBsAg loss was significantly higher in the discontinued group than in the continued group after propensity score matching (p < 0.001), including HBeAg‐positive and HBeAg‐negative patients. Conclusions Patients who discontinued TDF had significantly higher rates of HBsAg loss than patients who discontinued entecavir, especially among the subgroups without HBV relapse after cessation of therapy. Comparision of HBsAg loss rates between patients who discontined entecavir and TDF therapy after PSM.