Central venous thrombosis is a potentially life-threatening complication in patients on long-term home total parenteral nutrition (HTPN). Lack of venous access due to recurrent thromboses can prevent delivery of life-saving nutritional support. The long-term anticoagulation management to prevent thromboses in patients with central venous catheters for HTPN has not been well established. We have reviewed the role of warfarin in reducing the incidence of thromboses and its safety in our HTPN patients. Ninety consecutive HTPN patients were studied retrospectively. Twenty-two thromboses occurred during 1312 patient-mo in 53 HTPN patients on minidose warfarin. A minidose of warfarin is defined as 1-2 mg and does not prolong the prothrombin time. Seven thromboses occurred over 619 mo in 18 patients on a therapeutic dose of warfarin (minidose compared to therapeutic dose, p > 0.05). A therapeutic dose of warfarin is a dose that increases the prothrombin time to 1.2-1.5 times that of control. Twelve patients who had 18 thromboses in 323 patient-mo while on minidose warfarin were subsequently converted to therapeutic warfarin. The incidence of thromboses decreased to 2 in 369 patient-mo (p < 0.005). There were no hemorrhagic complications in the minidose warfarin group and four nonfatal hemorrhagic complications in the therapeutic dose warfarin group (p > 0.05). A therapeutic dose of warfarin is effective in reducing the incidence of thromboses in patients who experience central venous thrombosis despite minidose warfarin with a minimal increase in hemorrhagic complications.