WHAT IS KNOWN AND OBJECTIVE: One case report demonstrated warfarin resistance associated with sulphasalazine therapy. Our objective is to report on a case of warfarin potentiation rather than resistance, associated with sulphasalazine therapy. CASE SUMMARY: The patient was taking warfarin for two mechanical heart valves and was prescribed sulphasalazine for inflammatory bowel disease. He had stable international normalized ratios (INRs) before sulphasalazine administration. Approximately 3 weeks after starting sulphasalazine, he presented to the anticoagulation clinic with bruising and an INR of 6.1. The sulphasalazine was stopped, and the warfarin was held for 3 days; then the previous dose was resumed. Three weeks later, the INR returned to a therapeutic level. WHAT IS NEW AND CONCLUSION: This is the first case of sulphasalazine potentiating the effect of warfarin. Sulphasalazine may potentiate the hypoprothombinemic effect of warfarin.