A 32-year-old woman with a history of deep vein thrombosis (DVT), steroid-dependent ulcerative colitis, and osteoporosis was prescribed azathioprine for a steroid-sparing effect. Stable, therapeutic international normalized ratios (INRs) were obtained with warfarin 35 mg/week during a 6-week postpartum course to treat an initial DVT. Ten days after completing warfarin therapy, azathioprine was begun. A recurrent DVT occurred 9 days later, and an increase in warfarin dosage to 120 mg/week was necessary to achieve an INR of 2.0-3.0. The patient denied changes in warfarin adherence, dietary vitamin K intake, or medical conditions. The addition of azathioprine was the only change in her regimen. Review of the literature found only limited reports of an interaction between warfarin and azathioprine, with increases in warfarin requirements of 3-4 times. Careful monitoring and caution are recommended when administering these two drugs concomitantly.