Abstract Background and Aims Uremic toxins which are retained in ESRD include small solutes to large middle molecules. Large middle molecules play significant roles in immune modulation and cardiovascular morbidity and mortality. Expanded hemodialysis (HDx) enabled by innovative medium cut-off (MCO) membrane more effectively removes large uremic toxins vs current dialytic therapies. Aims: To evaluate the efficacy of MCO dialyzer in large middle molecules removal and pre-dialysis albumin levels after 24 weeks of treatment. Method This was an exploratory, prospective observational, multicenter cohort study. Prevalent patients on HD therapy for at least 90 days at the Renal Care Services (RCS) were included between June 6, 2018, to June 14, 2018. Uremic toxins removal was evaluated by measuring the reduction ratio (RR) of free light chains (FLC) κ, λ, Interleukin (IL) 6, IL-10, β2 Microglobulin (β2 M) and fibroblastic factor 23 (FGF-23) at 12 weeks ( w) of treatment, as well as the change in predialysis midweek serum level of β2M, FGF-23, factor XIV activity, and VII at baseline, 12 w and 24 w of treatment. A mixed-model repeated measures analysis (MMRM) was performed to identify statistical differences over time Results The RR of κ-FLC, λ-FLC, β2 M, and FGF-23 at week 12 showed a reduction between 46-72%; while in IL-6 RR was not significantly changed (Table 2). Predialysis serum levels decreased for β2m, FLCs and IL-6 and FGF 23 (Table 3). The decrease in albumin was within 5% from baseline. Twenty-two adverse events (AEs) occurred during the follow-up period; No AEs during HDx were deemed related to MCO membrane use. Conclusion MCO dialyzers are safe and effective in removing large MMs and decrease in the uremic toxins levels.