Unfractionated heparin (UFH) is used intraoperatively as antithrombotic by most vascular surgeons worldwide during infrainguinal bypass surgery (IABS) to reduce the risk of peroperative and early graft thrombosis. To reduce the harmful side effects of UFH (bleeding complications, HIT) and to reduce peroperative and early graft failure, other pharmaceuticals have been suggested for IABS. A systematic review was performed using MEDLINE, EMBASE and Cochrane databases. Only 9 studies on IABS and intraoperative antithrombotic use were eligible for review. Between studies heterogeneity was high and investigated study populations were often of small size. No study was retrieved comparing UFH to no-UFH. Dextran, human antithrombin and iloprost showed no beneficial effect compared to UFH alone for patency, mortality and morbidity. Low molecular weight heparin (LMWH) has potential benefits compared to UFH, but a statistically significant effect could not be demonstrated from the current review. The use of UFH during IABS to prevent intraoperative graft thrombosis has not been proven in randomized clinical trials. Dextran, human antithrombin and iloprost showed to be of no added beneficial effect for the patient compared to UFH alone. Data on the use of LMWH instead of UFH are promising, but no statistically significant benefit could be reproduced from literature. Results from a recent Cochrane review were favourable for LMWH, but it appeared that included data were not complete in that review. Randomized controlled trials are required for intra-operative use of antithrombotics and to improve peroperative and early patency after IABS.