Expanded hemodialysis (HDx) provides increased clearance of conventional and large middle molecules through innovative medium cutoff (MCO) membranes. However, there is a paucity of real‐world data regarding the benefits and safety of HDx. This large observational study evaluated outcomes among patients in Colombia undergoing HDx at a extended dialysis clinical services provider. This was a prospective single cohort study of prevalent patients who were treated with HDx; baseline information was collected from the most recent data before patients were started on HDx. Patients were followed prospectively for 1 year for changes in serum albumin and other laboratory parameters compared with the baseline. Survival, hospitalization and safety were assessed from the start of HDx. A total of 1000 patients were invited to enroll; 992 patients met the inclusion criteria for data analysis and 638 patients completed the year of follow‐up. Seventy‐four (8%) patients died during 866 patient‐years (PY) of follow‐up; the mortality rate was 8.54 deaths/100 PY (95% confidence interval [CI], 6.8‐10.7). There were 673 hospitalization events with a rate of 0.79 events/PY (95% CI, 0.73‐0.85) with 6.91 hospital days/PY (95% CI, 6.74‐7.09). The observed variability from baseline and maximum average change in mean serum albumin levels were −1.8% and −3.5%, respectively. No adverse events were related to the MCO membrane. HDx using an MCO membrane maintains stable serum albumin levels and is safe in terms of nonoccurrence of dialyzer related adverse events.