BACKGROUND: People using prescription medication often concurrently take herbal supplements. In a case report, the anticoagulant effect of warfarin decreased after patients consumed ginseng. OBJECTIVE: To evaluate the interactions between American ginseng and warfarin. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: General Clinical Research Center, University of Chicago, Chicago, Illinois. PARTICIPANTS: 20 healthy patients. INTERVENTION: In this 4-week study, 20 patients received warfarin for 3 days during weeks 1 and 4. Beginning in week 2, patients were assigned to receive either American ginseng or placebo. MEASUREMENTS: International normalized ratio (INR) and plasma warfarin level. RESULTS: The peak INR statistically significantly decreased after 2 weeks of ginseng administration compared with placebo (difference between ginseng and placebo, -0.19 [95% CI, -0.36 to -0.07]; P = 0.0012). The INR area under the curve (AUC), peak plasma warfarin level, and warfarin AUC were also statistically significantly reduced in the ginseng group as compared with the placebo group. Peak INR and peak plasma warfarin level were positively correlated. LIMITATIONS: The study sample consisted of young, healthy volunteers in a research setting rather than patients taking therapeutic doses of warfarin. CONCLUSIONS: American ginseng reduces warfarin's anticoagulant effect. When prescribing warfarin, physicians should ask patients about ginseng use.