Recent guidelines do not recommend antithrombotic prophylaxis (AP) to prevent catheter-related thrombosis in cancer patients with a central line. This study assessed the management of central lines in cancer patients, current attitude towards AP, catheter-related and systemic venous thromboses, and survival. Of 1410 patients enrolled, 1390 were seen at least once in the 6-month median follow-up. Continuous AP, mainly low-dose warfarin, was given to 451 (32.4%); they were older, with a more frequent history of venous thromboembolism (VTE), and more advanced cancer. There was no difference in catheter-related thrombosis in patients given AP or not (2.8% and 2.2%, odds ratio 1.29, 95% confidence interval 0.64-2.6). The median time to first catheter-related complication was 120 days. Systemic VTE including deep and superficial thromboses and pulmonary embolism, were less frequent with AP (4% versus 8.2%, P = 0.005). Mortality was also lower (25% versus 44%, P = 0.0001). Multiple logistic regression analysis found only advanced cancer and no AP significantly associated with mortality. No major bleeding was recorded with AP. Current AP schedules do not appear to prevent catheter-related thrombosis. Systemic VTE and mortality, however, appeared lower after prophylaxis.