Background: The role and dose of anticoagulants in thrombosis prophylaxis for cancer patients with central venous catheters (CVCs) is controversial. Methods: 1590 cancer patients receiving chemotherapy via CVCs were randomised to no warfarin [control] vs warfarin [either daily fixed dose 1mg warfarin (FDW) or daily dose adjusted warfarin (DAW) to maintain International Normalised Ratio between 1.5 and 2.0]. Clinicians ‘certain’ of the benefit of warfarin randomised between FDW and DAW. The primary outcome measure is the incidence of radiologically proven, symptomatic catheter-related thrombosis (CRT); secondary outcome measures include toxicity, incidence of all thromboses and overall survival. Findings: Compared to control, warfarin (79% FDW; 21% DAW) reduced neither CRT [5.9% vs 5.9%; relative risk (RR) 0.99, (95% Confidence Interval (CI) 0.57-1.72), p=0.98] nor all thrombotic events [7.4% vs 9.4%; RR 0.78 (95%CI 0.50-1.24), p=0.30]. However, compared to FDW only, DAW was superior in preventing CRT [2.8% vs 7.2%; RR 0.38, (95%CI 0.20-0.71), p=0.002] but not all thromboses [5.5% vs 7.9%; RR 0.70 (95%CI 0.43-1.14), p=0.15]. Major bleeding events were rare; an excess was observed with warfarin compared to control (7 vs 1, p=0.07) and with DAW compared to FDW (16 vs 7, p=0.09). A combined endpoint of thromboses and major bleeding showed no difference between warfarin and control or between DAW and FDW. No survival difference was demonstrated in either comparison. Interpretation: Thrombosis rates were low (5.3%); there is no benefit in using warfarin in comparison to no warfarin for the prophylaxis of symptomatic CRT or other thromboses in cancer patients.