Heparin-free hemodialysis (HF-HD) has been increasingly used in patients at risk for bleeding, especially in the intensive care unit (ICU). Lack of heparin can reduce solute clearances in continuous hemofiltration; the effect on HD is undefined. Failure to recognize an effect of the anticoagulation strategy upon delivered clearance could contribute to the known problem of underdialysis in the ICU. In addition, the consequences of "locking" dialysis catheters with concentrated heparin solutions are also unclear. This study was designed to define the clinically relevant consequences of HF-HD and catheter locking. In part I, we performed 200 HD treatments on inpatients, of which 100 were performed with heparin, and 100 were performed as HF-HD. We calculated prescribed and delivered Kt/V and dialysis efficiency. In part II, a separate group of 14 patients undergoing HF-HD via central venous catheters had measurement of activated partial thromboplastin time (aPTT) during the last hour of dialysis, as well as 15, 60, and 240 min after catheters were locked with 1:5000 heparin. The prescribed Kt/V was 1.74+/-0.31 for standard HD with heparin vs. 1.66+/-0.36 for HF-HD (p=ns). The delivered Kt/V was 1.42+/-0.32 vs. 1.36+/-0.38 (p=ns). Efficiency was 0.82 vs. 0.84 (p=ns). Baseline aPTT was 28+/-5 s, and increased to 126+/-54 s, 15 min after locking (p<0.0001) and to 71+/-50 s, 60 min after locking (p=0.005). By 240 min, the mean aPTT had fallen to 33+/-9 s (p=0.03), although individual values were still as high as 50 s. The HF technique does not compromise delivery of dialysis to inpatients. Increased treatment time is not necessary. Locking catheters with heparin after HF-HD resulted in prolonged unintentional anticoagulation.