Anti-vitamin K drugs are widely used as anticoagulant in human thromboembolic diseases. Similar compounds have also been used as rodenticides to control rodent population since 1950s. Massive use of first generation anticoagulants, especially warfarin, has lead to the development of genetic resistances in rodents. Similar resistances have been reported in human. In both cases, polymorphisms in VKORC1 (Vitamin K epoxide reductase subunit 1), the subunit 1 of the VKOR (Vitamin K epoxide reductase) complex, were involved. In rats (Rattus norvegicus), the Y139F mutation confers a high degree of resistance to warfarin. Little is known about the in vitro consequences of Y139F mutation on inhibitory effect of different anticoagulants available. A warfarin-susceptible and a warfarin-resistant Y139F strain of wild rats (Rattus norvegicus) are maintained in enclosures of the Lyon College of Veterinary Medicine (France). Using liver microsomes from susceptible or resistant rats, we studied inhibition parameters by warfarin (Ki = 0.72 ± 0.1 μM; 29 ± 4.1 μM), chlorophacinone (Ki = 0.08 ± 0.01 μM; 1.6 ± 0.1 μM), diphacinone (Ki = 0.07 ± 0.01 μM; 5.0 ± 0.8 μM), coumachlor (Ki = 0.12 ± 0.02 μM; 1.9 ± 0.2 μM), coumatetralyl (Ki = 0.13 ± 0.02 μM; 3.1 ± 0.4 μM), difenacoum (Ki = 0.07 ± 0.01 μM; 0.26 ± 0.02 μM), bromadiolone (Ki = 0.13 ± 0.02 μM; 0.91 ± 0.07 μM), and brodifacoum (Ki = 0.04 ± 0.01 μM; 0.09 ± 0.01 μM) on VKOR activity. Analysis of the results leads us to highlight different anticoagulant structural elements, which influence inhibition parameters in both susceptible and Y139F resistant rats.