The impact of treatment on health related quality of life (HRQoL) in CHB patients is unclear. OBJECTIVE: The objective of this study was to compare the changes in HRQoL from baseline, as measured by changes in health status using the EuroQoL 5 Dimensions (EQ-5D) questionnaire, in patients receiving ETV or LAM treatment. Utility scores are anchored between full health (1) and death (0). METHODS: This was a randomized double blind, double dummy, active controlled trial. Questionnaires were administered prior to the physician visit at baseline, Weeks 24 and 48. Mean changes in health index score (HIS) and visual analog scale (VAS) score from baseline were calculated in all treated patients. Proportions of patients who had improvement or no change in health dimensions were compared between the two treatment groups, and patients with missing Week-48 data were considered failures (NC=F). RESULTS: A total of 116 of 141 (82%) ETV and 114 of 145 (79%) LAM patients completed the questionnaires at baseline. Though ETV patients demonstrated a clinically meaningful improvement in HIS (0.03) and LAM patients did not (0.01), the difference (0.02) was not statistically significant (p=0.12). ETV patients had a trend towards better change in VAS at Week-48 (ETV=4.13; LAM=0.91; mean difference estimate ETV-LAM= 2.11; p=0.21). A larger proportion of ETV patients had improvement or no change in all five health dimensions at Week-48. ETV treatment was superior to LAM in the following dimensions: mobility; self care; pain or discomfort (94% vs. 82%, p=0.007; 94% vs. 85%, p=0.03; and 90% vs. 77%, p=0.01, respectively). CONCLUSION: ETV therapy was associated with greater proportions of patients with improvement or no change in mobility, self care, and pain or discomfort after 48-weeks of treatment. ETV patients demonstrated a clinically meaningful improvement in HIS, and greater improvement in VAS from baseline compared to LAM.