It has been reported that clot formation may occur when blood is mixed directly with nonionic contrast medium in a syringe during angiography. To investigate this possibility, we performed three in vitro experiments to determine the anticoagulant properties of a low-osmolar, nonionic contrast medium (iohexol); a low-osmolar, ionic medium (ioxaglate); and a high-osmolar, ionic medium (diatrizoate). In the first experiment, human arterial blood was incubated at room temperature in an angiographic syringe with each of the three media for 60 min, after which the mixture was filtered for clots. In the second experiment, the clotting times of venous blood in heparinized saline or serial dilutions of the three agents were determined. In the third experiment, the partial thromboplastin time of platelet-poor plasma in heparinized saline or serial dilutions of the three agents was measured. No clots were observed in any of the arterial blood samples. Iohexol prolonged the normal 15-min clotting time of venous blood to 160 min, compared with a clotting time of at least 330 min for ioxaglate and diatrizoate. Iohexol prolonged the normal 36-sec partial thromboplastin time of platelet-poor plasma to 40 sec, compared with 50 sec for diatrizoate and 54 sec for ioxaglate. Our data show that iohexol, like ioxaglate and diatrizoate, inhibits clot formation when mixed with blood in a syringe. It prolongs the clotting time to approximately the same degree as 600 U/l of heparinized saline, but to a lesser degree than the other two media. All three media have a minimal effect on the partial thromboplastin time. Our results do not show any risk of clot formation in the usual clinical setting in which there is inadvertent mixing of blood with iohexol, ioxaglate, or diatrizoate in an angiographic syringe.