We investigated tissue factor pathway inhibitor (TFPI) levels in 44 non-dialysis uremic patients and 36 chronic dialysis patients, as well as the changes of TFPI levels during hemodialysis sessions using heparin (n = 14), low molecular weight heparin (n = 7), nafamostat mesilate (n = 5), and argatroban (n = 2). In non-dialysis uremic patients, TFPI levels increased (mean +/- SD: 178 +/- 37% of control pooled plasma) along with the impairment of renal function. In chronic hemodialysis patients, TFPI levels were even higher (265 +/- 72%) before dialysis, but did not depend on the etiology of renal failure (diabetic or non-diabetic), the interval between dialysis sessions (twice or three times a week), and the duration of hemodialysis. During hemodialysis sessions using heparin, TFPI levels increased 1.2- to 3.5-fold compared with the level before hemodialysis and the degree of increase in TFPI was correlated with the heparin concentration (r = 0.648, p = 0.0001, n = 29). During dialysis sessions using low molecular weight heparin, TFPI levels also increased, but the change was less marked than during dialysis with heparin. TFPI levels did not change during dialysis sessions using nafamostat mesilate or argatroban. In conclusion, TFPI levels were increased by renal failure and by long-term repeated injection of heparin, but the hemodialysis procedure itself did not alter the TFPI level.