Warfarin, an anticoagulant with a narrow therapeutic window, is largely metabolized by cytochrome P450 2C9. Isopropyl alcohol has been shown to inhibit the activity of this enzyme. Use of topical isopropyl alcohol as a rubefacient may place patients at risk for systemic exposure. Isopropyl alcohol's effect on the international normalized ratio (INR) has not been well characterized. We describe five patients who experienced INR elevations after topical application of isopropyl alcohol. Each patient's INR was therapeutic for at least seven visits prior to becoming supratherapeutic. All patients confirmed drug adherence and denied medication or dietary changes. Seventy percent isopropyl alcohol was used in all cases over a large body surface area of intact skin multiple times daily for several days. All patients experienced a 10% or greater increase in their INR compared to previous levels. On discontinuation of isopropyl alcohol, each patient's INR returned to and remained in therapeutic range for the next 2 months. Prediction of isopropyl alcohol's effect of the INR is confound by several factors, notably the BSA covered, concentration of alcohol in the product, contact time with the skin, and skin integrity. It is important that clinicians inquire about the use of isopropyl alcohol and educate patients about its potential risk in those receiving warfarin therapy.