Drug-drug interactions are most commonly occurring phenomenon in clinical practice. Many physicians are afraid of being involved in an allegation of malpractices due to the occurrence of any severe interaction. These interactions not only occur between drugs but also between any kind of food, tobacco smoke, caffeine and alcohol etc. Therefore, the present study was directed to inspect the effect of caffeine on the anticoagulation activity of warfarin in healthy adult male albino rabbits. Blank blood samples were collected from each rabbit. Rabbits were given warfarin (0.5mg kg-1) orally via stomach tube and blood samples were collected in PT/INR vials at various intervals. After a washout period of 14 days, warfarin was orally administrated at same dose rate along with caffeine (5 mg kg-1 every twelve hours for three days) and same sampling schedule was repeated. Prothrombin time (PT) and the international normalized ratio (INR) of blood samples were determined to estimate changes in the anticoagulation activity of warfarin after its concurrent administration with caffeine. The PT data revealed that Rmax and AUC increased significantly (P<0.05) from 1991.6 and 60.5 to 2124.8 and 67.5, respectively, before and after co-administration. Similarly, a significant (P<0.05) increase was observed in Rmax and AUC of INR from 6.42 and 153.7 to 7.4 and 167.5, respectively, alone and along with caffeine. However, no change was observed in Tmax associated with PT and INR either the drug was administered alone or in combination with caffeine. It was concluded that caffeine has the capacity to inhibit the metabolism of warfarin and enhance its plasma concentration and hence anticoagulant effects. Thus, patients should be advised to limit the frequent use of caffeine-rich products i.e. tea and coffee during warfarin therapy.