OBJECTIVES: In Turkey, lamivudine (LAM) is the only reimbursed antiviral (AV) agent for the treatment of chronic hepatitis B (CHB) patients with HBV-DNA level < 107 copies/mL. Tenofovir (TDF) can be added when the patient does not respond at week24, or viral resistance emerges. This study aimed to compare the long-term clinical outcomes of telbivudine (ldt) with or without TDF add-on and LAM with or without TDF add-on in the treatment of CHB. METHODS: Analysis population consisted of patients (n=1000; 35% HBeAg-positive; 35 years old) without compensated or decompensated cirrhosis(CC, DC) or hepatocellular cancer(HCC). AVs compared were 1) Ldt 600mg/day; 2) Ldt + add-on TDF 300mg/day when non-response or viral resistance occurs; and 3)LAM 100mg/day (4)LAM + add-on TDF 300mg/day. A decision tree model with 5 parallel pathways for different levels of HBV-DNA was built using a 10-year time-horizon. Selected major clinical outcomes were mortality and life-years-lost (LYL). RESULTS: With LAM or Ldt monotherapy, 137CC, 5DC, 40 HCC cases and 70 dead versus 85CC, 3,5DC and 25HCC cases and 44 dead were expected to occur, respectively. With LAM or Ldt monotherapy, 1236 and 774 life-years will be lost, respectively. When a potent AV is added to LAM or Ldt, HBV complications were expected to decrease and avoided LYL were substantial (164 to 591 years, respectively). However, there is no important difference between starting with LAM or Ldt and adding TDF strategies: 1CC, 0 DC, 0HCC cases and 2 dead will be avoided. CONCLUSIONS:   Ldt monotherapy was found to be superior to LAM monotherapy. However, Ldt +TDF does not seem a better approach than LAM+TDF in the treatment of CHB. This paradoxical finding might be explained due to marginally superior efficacy of Ldt versus LAM and a longer time-period before adding a potent antiviral to treatment.