Abstract Background and Aims The global prevalence and incidence of maintenance dialysis are increasing. Among the modalities of RRT, maintenance hemodialysis (HD) has been a major method worldwide for patients with end-stage renal disease (ESRD). The recent introduction of online-hemodiafiltration (OL-HDF) may offer major advantages in clearing molecules of various sizes, reducing HD-associated amyloidosis and chronic inflammation. Because this modality has been officially approved for ESRD patients, the number of patients worldwide undergoing OL-HDF therapy have consistently increased. However, evidence of clinical effects of OL-HDF is scarce. In this study, we investigated changes in laboratory values over more than 12 months after switching to OL-HDF. Method The present study included data from a K-cohort (CRIS no. KCT0003281) of prospectively enrolled adult patients with ESRD undergoing hemodialysis in 6 tertiary hospitals in South Korea. A total of 435 patients was recruited, and 339 patients were on HD at the beginning of the study period. Among the 339 patients, 182 were followed up for more than 24 months. During the follow-up period, 135 patients remained on HD and 47 switched to HDF. However, 3 of the 47 who switched to HDF later returned to HD. We compared clinical parameters in 44 patients who switched to OL-HDF and 135 patients who remained on HD (Figure 1). We used a paired t-test to compare baseline and 24-month follow-up results. Results The mean age of the study subjects was 61.2 ± 12.2 years, and 62.6% were male. The duration of dialysis was 2.9 ± 4.4 months. In the group that was switched from HD to OL-HDF, the levels of Hgb and serum albumin increased significantly (10.46 ± 1.03 vs. 11.08 ± 0.82, P = 0.001, and 3.73 ± 0.29 vs. 3.87 ± 0.30, P = 0.001, respectively). Although the normalized protein catabolic rate (nPCR) decreased from baseline after 24 months, the change was not significant (1.07 ± 0.25 vs. 1.03 ± 0.21, P = 0.433). Calcium and calcium-phosphorus products also increased significantly after OL-HDF therapy (8.32 ± 0.75 vs. 8.75 ± 0.80, P < 0.001 and 41.89 ± 12.62 vs. 50.80 ± 20.79, P = 0.013, respectively). To determine possible confounding effects of clinical factors, we conducted a linear regression analysis with multiple adjustments for changes in various laboratory values after HDF conversion. Conversion to HDF resulted in elevation of serum calcium and albumin levels, both of which were significant even after adjustment for baseline demographics, inflammation, and dialysis duration. Conclusion In conclusion, long-term OL-HDF treatment over 12 months or longer was associated with no detrimental effects on anemia or nutritional status. To investigate the effects of OL-HDF therapy, evaluating more parameters over a longer follow-up period with a larger number of patients is needed. Figure 1.