Aims: The major metabolite of sofosbuvir (SOF), GS-331007, is cleared renally and tends to accumulate in patients with chronic kidney disease (CKD). However, there are a substantial amount of data showing that this accumulation is not clinically significant, even in patients with end stage renal disease. Methods: This retrospective analysis of 37 Phase 2 and 38 Phase 3 studies presents the safety profile of SOF-based therapies (LDV/SOF, SOF/VEL and SOF/VEL/VOX) in patients with mild to moderate CKD as well as in patients with normal renal function. Results: 8,181 patients were included in this analysis. Mean baseline eGFR was 118.2, 69.3, and 43.6 mL/min/1.73m2 for patients with normal renal function (n=6575), mild (n=1499), or moderate (n=107) renal impairment, respectively. The mean eGFR at post-treatment follow-up week 4 was 114.4, 69.9, and 46.3 mL/min/1.73m2 for patients with normal renal function (n=5519), mild (n=1285), or moderate (n=90) renal impairment, respectively. When comparing baseline levels with those of post-treatment follow-up week 4, there was no clinical difference observed. Baseline characteristics were generally similar across groups, except patients with impaired renal function were older. Table 1 provides a summary of adverse events (AEs). Rates of Grade 3-4 AEs and discontinuations due to AEs were similar across groups. Patients with moderate renal impairment had higher rates of SAEs but most were not treatment-related. Conclusions: Sofosbuvir-based regimens were safe and well-tolerated in patients with mild or moderate renal impairment. Renal function remained stable throughout treatment, and similar rates of AEs were observed across all treatment groups.