Introduction: Recurrent Clostridium difficile infection (rCDI) is an urgent public health threat that is associated with significant mortality, substantial medical costs, and decreased quality of life. Microbiota therapy is gaining acceptance to prevent rCDI in multi-recurrent patients. RBX2660, a standardized microbiome-based therapeutic, was previously reported to show efficacy in rCDI prevention in a ran-domized, double-blind, placebo-controlled Phase 2B clinical study (PUNCH CD2). Herein, we evaluated this Phase 2B study data to determine how quality of life (QoL) assessment was associated with RBX2660 treatment. Methods: Subjects enrolled in the double-blinded, placebo-controlled multi-center Phase 2B clinical study were randomized to receive either 2 RBX2660 doses (Group A), 2 placebo doses (Group B) or 1 RBX2660 dose + 1 placebo dose (Group C) via enema, with doses delivered 7 days apart. Enrolled subjects had >2 prior rCDI or >2 prior CDI episodes requiring hospitalization. The primary efficacy endpoint was absence of CDI at 8 weeks from the last dose. The validated SF-36 was used to identify changes to health-related QoL following study treatment. QoL was assessed at Baseline and at weeks 1, 4 and 8 following blinded treatment, and were compared within and across treatments using unpaired t-test. Each component is analyzed on a 0-100 scale with a higher score representing an increase to QoL. Results: The Baseline results for the mean Physical Component Score (PCS) and Mental Component Score (MCS) were comparable across arms, and there were no statistically significant differences at base-line between subjects who later responded to treatment and those who did not. By week 1, statistically significant and clinically important differences were noted for the MCS within each group compared to Baseline scores and were maintained through 8 weeks. Overall, both the mean PCS and MCS improved after treatment across all groups. There were no significant differences identified between treatment groups. Conclusion: The similarity among Baseline SF-36 QoL scores confirms a uniform population among treatment groups. The statistically significant SF-36 increase after treatment underscores the potential QoL benefit for preventing rCDI, even as early as one week after treatment. Larger studies will be needed to confirm these results and to detect a significant difference in QoL scores between RBX2660- and placebo-treated participants.