We present a case in which thrombus formation on a guidewire was visualized during intravascular ultrasound imaging despite the administration of 10,000 units of heparin sulfate prior to the procedure. Gross thrombus formation was confirmed upon removal of the guidewire. The activated clotting time was found to be 191 s, suggesting heparin resistance. This report graphically illustrates the potential thrombogenicity associated with intravascular guidewire manipulation during procedures such as intravascular ultrasound imaging and percutaneous transluminal coronary angioplasty. Moreover, this case suggests that adequate heparinization should be routinely verified by measuring the activated clotting time prior to introducing a guidewire into the arterial system.