The aim of this study was to investigate the possible influence of single-dose 2.0-g azithromycin (AZ-ER) on anticoagulation in patients taking warfarin. Eighteen consecutive patients receiving long-term stable warfarin therapy were enrolled in this study. AZ-ER was administered 1 hour prior to tooth extraction. The international normalized ratio (INR) value was measured prior to AZ-ER administration as well as during, 1 day after, and 7 days after the tooth extraction. Additionally, the azithromycin concentration in the extraction wound as well as in the peripheral venous blood was assessed. The changes in INR throughout the study period were not statistically significant (2-factor analysis of variance, NS). The azithromycin concentration in extraction wounds was higher than that in peripheral veins. The results of this study suggest that prophylactic administration of AZ-ER to patients receiving daily warfarin therapy with a stable coagulation status has no relevant effect on the anticoagulant effect of warfarin.