When arterial blood samples for activated clotting time (ACT) are difficult to obtain from the arterial sheath during coronary intervention, venous ACT serves as a substitute. Data are lacking on whether arterial and venous ACT are identical and whether one can serve as an effective substitute for the other. Forty-eight patients undergoing percutaneous transluminal coronary angioplasty (PTCA) were prospectively evaluated to answer this question. Simultaneous arterial and venous ACT samples were drawn from femoral artery and vein vascular sheaths before and during each procedure, and ACT values were determined with a Hemochron automated electronic timer. Porcine heparin dosing was guided by arterial ACT in the first 25 patients and by venous ACT in the last 23 patients. The target ACT value used for continued heparin dosing was 400 sec. At baseline and throughout the study up to 60 min, venous ACT was slightly and significantly greater than arterial ACT. Despite this statistical difference in ACT values, there was no difference in complication rate between the two groups, and the amount of heparin used during either guiding regimen was the same. Therefore, although venous ACT values are slightly higher than arterial, the more convenient venous ACT can be safely used to guide heparin dosing during PTCA when using a target ACT value of 400 sec.