Abstract: This study determined the changes in international normalized ratio (INR) that occur during hemodialysis (HD) treatment of patients receiving warfarin. Twenty patients were enrolled in the study (15 males, 5 females; mean age, 71 ± 7 years). We investigated changes in INR and R-isomer and S-isomer of warfarin concentrations before (pre-) and after (post-) HD. Post-HD INR levels were significantly decreased compared with pre-HD levels (P < 0.01), whereas plasma concentrations of both R-isomer and S-isomer of warfarin were significantly increased post-HD compared with pre-HD (P < 0.01). There was a negative correlation between INR changes and changes in warfarin concentration or changes in serum albumin levels during HD. Multivariate analysis revealed that change of serum albumin was the only factor that was significantly related to the change of INR (P = 0.0051, R2 = 0.501). We suggest that the free fraction of plasma warfarin decreased with increases in serum albumin levels because the protein-binding rate of warfarin is very high and free fractions were bound to albumin during HD sessions. The INR depletion was therefore dependent on circulating plasma volumes and serum albumin concentrations. Caution should be taken for those HD patients who have absolute indications of anticoagulation therapy with warfarin.