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Resveratrol (RVT) has various beneficial bioactivities and popularly used as a dietary supplement. RVT showed inhibitions on CYP1A2/2C9/3A4, breast cancer resistance protein (BCRP), and some conjugated metabolites of RVT also inhibited BCRP. (±)Warfarin, an anticoagulant for cardiovascular disease but with narrow therapeutic window, were substrates of CYP1A2/3A4(R-form), 2C9(S-form) and BCRP. We hypothesized that the concurrent use of RVT might affect the metabolism and excretion of warfarin. This study investigated the effect of RVT on the pharmacokinetics and anticoagulation effect of (±)warfarin. Rats were orally given (±)warfarin (0.2 mg/kg) without and with RVT (100 mg/kg) in a parallel design. The results showed that RVT significantly increased the AUC0−t of S-warfarin and international normalized ratio. Mechanism studies showed that both RVT and its serum metabolites (RSM) inhibited BCRP-mediated efflux of R- and S-warfarin. Moreover, RSM activated CYP1A2/3A4, but inhibited CYP2C9. In conclusion, concomitant intake of RVT increased the systemic exposure of warfarin and enhanced the anticoagulation effect mainly via inhibitions on BCRP and CYP2C9. [ABSTRACT FROM AUTHOR]