OBJECTIVES: An all-oral HCV therapy, ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV), without ribavirin (RBV), has been approved by the Food and Drug Administration (FDA) for treatment of treatment naïve, non-cirrhotic, GT1b adults. We report the HRQoL impact of OBV/PTV/r+DSV, with and without RBV, after 12-week treatment in the Phase 3 PEARL-III trial. METHODS: HCV patients were randomized in a 1:1 ratio to OBV/PTV/r+DSV with RBV or OBV/PTV/r+DSV without RBV and treated during a 12-week double-blind period. HRQoL was assessed using the SF-36 v2 Health Survey (SF-36) which was administered to patients at baseline, during treatment, at end of treatment (EOT) and at post-treatment (PT) visits. Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were calculated for the SF-36. The statistical significance of differences between treatment groups in mean change from baseline to EOT was assessed. RESULTS: The analysis included 210 patients on OBV/PTV/r+DSV with RBV and 209 on OBV/PTV/r+DSV without RBV. Among non-cirrhotic subjects with GT1b infection who were treated with OBV/PTV/r+DSV without RBV, almost no decrements from baseline PCS or MCS scores were observed at EOT (changes [mean±SD] of -0.1±6.71 in PCS and -0.1±9.09 in MCS). The decrements OBV/PTV/r+DSV with RBV were numerically larger (-0.5±6.80 in PCS and -1.4±9.15 in MCS); however, differences from the non-RBV group were not statistically significant for either PCS or MCS (p-value=0.348 in PCS and p-value=0.150 in MCS). At PT week 24, mean changes from baseline were 1.0±6.20 in PCS and 1.9±8.40 in MCS in the non-RBV group 0.9±6.04 in PCS and 1.8±7.40 in MCS in the RBV group. CONCLUSIONS: At the end of 12-week treatment in PEARL-III, the interferon-free all-oral OBV/PTV/r+DSV regimen in treatment-naïve GT1b patients had negligible impact on patient HRQoL, regardless of whether RBV was co-administered. After treatment, PCS and MCS scores for both treatment groups showed similar improvement over baseline.