BACKGROUND Defibrotide (Def), a new antithrombotic drug, has been proposed as a prophylactic agent in postoperative DVT. Most of the studies to date, however, have either not been controlled or have used unverifiable systems for asymptomatic DVT diagnosis. This randomized pilot study compared Def versus standard low-dose calcium heparin (CH) prophylaxis after gynaecological surgery, using objective criteria for DVT diagnosis. METHODS Forty-one pts received 400 mg Def intramuscularly twice a day starting the day before surgery; 40 pts received 5000 IU CH s.c. twice daily beginning 2h before surgery. The two groups were well matched for all relevant risk factors. DVT was diagnosed by means of the 125I fibrinogen uptake test (FUT) and venography. Blood coagulation and fibrinolysis tests were also carried out perioperatively. RESULTS Isotopic DVT (FUT-positive for two consecutive days) was recorded in 6 (14.6%) of the Def and 5 (12.5%) of the CH groups. In cases where FUT was positive for at least three consecutive days (4 in Def and 1 in CH), venography confirmed DVT in 3 cases (all in the Def group). No side-effects were recorded in either group and the amounts of transfused blood were not different. No significant differences in blood coagulation or fibrinolysis tests were recorded, except for higher fibrinogen levels on the 8th post-operative day in the Def group. CONCLUSIONS These results do not indicate any trend suggesting that Def, as a prophylactic agent in gynaecological surgery, offers any clinical or practical advantages over standard low-dose heparin prophylaxis.