Background and Aims: Hepatitis flares due to chemotherapyinduced HBV reactivation in lymphoma patients with resolved HBV infection can be life-threatening but the optimal preventive strategy is unknown. Methods: Decision tree analysis was done to compare the cost of 2 comparators (A, prophylactic antiviral therapy from the start of chemotherapy to 6 months after completion of chemotherapy; B, monthly HBVDNA monitoring and antiviral therapy for 48 weeks upon HBV reactivation) with current practice in hypothetic cohorts of lymphoma patients with resolved HBV infection who receive rituximab-containing chemotherapy. Probability of HBV-related events was estimated by published studies. The cost was calculated based on the perspective of National Health Insurance Program, Taiwan. Sensitivity analysis was performed to account for the impact of the efficacy and the cost of different interventions. Results: The treatment cost ranged from USD $1476.0 to $2993.1 for each patient, depending on the costs of antiviral therapy and HBVDNA test. One-way sensitivity analysis indicated that prophylactic antiviral therapy was more cost-saving if the cost of HBVDNA test was higher than USD $62.2/test. However, monthly HBVDNA follow-up was cost-saving if HBV reactivation rate of the target population was lower than 12.3%. The estimated cost of preventing one HBV-related hepatitis flare by prophylactic antiviral therapy was USD $21190.1 (range $15258.8 to $27121.5) if the probability of hepatitis flare was 10%. Conclusions: Characterization of high-risk groups for chemotherapy-induced HBV-related hepatitis flare is needed to increase the cost effectiveness of prophylactic antiviral therapy.