Tissue factor pathway inhibitor (TFPI) acts by complexing with tissue factor and factors VIIa and Xa to retard the extrinsic pathway of the coagulative process. The present study was designed to assess the antithrombotic properties of topically applied TFPI in a model of rabbit arterial thrombosis. A standardised, thrombogenic end-to-end anastomosis was made on the central ear artery. The anastomotic site was irrigated with vehicle (control, n = 5), TFPI 4 micrograms/ml (n = 8), TFPI 40 micrograms/ml (n = 8), or heparin 100 IE/ml (n = 7). The growing thrombus was observed under a stereo microscope. The image was displayed on a video monitor and recorded for analysis using computer assisted planimetry. Topical application of TFPI in either concentration or heparin did not change maximal thrombus size, mean thrombus size, or time to maximal thrombus size significantly when compared to the contralateral vehicle-treated ear. Significant anastomotic bleeding was observed in vessels treated with TFPI 40 micrograms/ml (p < 0.05).