Low-molecular-weight (LMW) heparin has recently been used for anti-coagulation in maintenance hemodialysis. The LMW heparin was administered as a single bolus in hemodialysis that usually lasted for four hours or less. The regimen for administering LMW heparin in hemodialysis of longer duration (5 hours or more) is not well documented and manufacturers recommend a supplementary dose equivalent to one-quarter of the initial dose to be given at 4 hours after the commencement of hemodialysis. In this study, we explored whether administering a single dose of LMW heparin is feasible in hemodialysis of longer duration. Maintenance five-hour hemodialysis sessions were performed in nine uremic patients with two different heparin regimens: single dose of LMW heparin (nadroparin) 12,500 ICU AXa at the beginning of dialysis or a priming dose of nadroparin 10,000 ICU AXa at the beginning of dialysis followed by a supplementary dose of nadroparin 2,500 ICU AXa at the beginning of the fifth hour of dialysis. Clots in the airtraps or clotting of the dialyser were not observed in hemodialysis with the single dose heparin regimen. The anti-Xa activities at different time intervals during dialysis were above the therapeutic range of 0.5 U/ml except towards the end of the hemodialysis treatment. There was no difference between anti-Xa activities determined in dialysis sessions using two different regimens of LMW heparin at any individual time interval. The anti-thrombotic effect determined by the area under the time response curve for anti-Xa activity was comparable in the two LMW heparin regimens. Hence, our findings suggest a single bolus dose of LMW heparin (nadroparin) at 12,500 ICU AXa provides adequate, safe, and effective anti-coagulation for five-hour hemodialysis. This practice is convenient and avoids the necessity of administering a double dose of LMW heparin.