Abstract: We studied the pharmacokinetics of nafamostat mesilate (NM) used as an anticoagulant in continuous hemodiafiltration (CHDF) with a polyacrylonitrile (PAN) membrane used as the hemofilter. Six patients undergoing CHDF for multiple organ dysfunction syndrome (MODS) were chosen as subjects. The inlet NM concentration measured 24 h after the start of CHDF was significantly greater than that after 1 h ( P = 0.0431). No significant difference was observed between the outlet NM concentration and the ultrafilter concentration at 1 h or 24 h after the start of CHDF. However, concentrations at 24 h differed significantly from concentrations at 1 h at all sites. Significant correlation was observed between the dose of NM and the outlet NM concentration ( P = 0.0475). No statistical correlation was observed between the dose of catecholamines and the outlet NM concentration ( P = 0.0985). This study is the first to disclose a mild but significant time‐dependent serum NM concentration in patients with MODS.