The prothrombotic effects of nonionic contrast media (NICM) have been evaluated in both biological and clinical studies. The question of whether there is a higher risk of thromboembolism during angiography with NICM than with ionic contrast media (ICM) has not yet been answered, nor has the precise role of the angiographic procedure per se in such complications been determined. The present study was performed to compare in vivo the potential prothrombotic effects during cardiac angiography of an NICM with those of an ICM, to estimate the effects of the procedure per se, and to assess how long these effects might be maintained. We measured blood levels of three markers of activation of blood coagulation: thrombin-antithrombin III (TAT) complexes, prothrombin fragment 1 + 2 (F1 + 2), and the split product of fibrin, D-dimer, before and after coronary angiography in three groups of patients. In group 1, 14 patients underwent coronary angiography with the NICM iopamidol 370. In group 2, 10 patients underwent coronary angiography with the ICM ioxaglate. In group 3, 10 patients were evaluated immediately after cardiac catheterization, before the injection of contrast material, as controls. No statistically significant differences between the three groups were found in TAT, F1 + 2, or D-dimer levels at different times before and after coronary angiography. There was a trend toward a transient increase in TAT levels after coronary angiography with iopamidol, which at first suggested a possible brief activation of hemostasis with this NICM, but a similar trend was also seen in the control group. We hypothesize that not only the type of contrast material, but also the angiographic procedure per se and patient-related factors all play roles in determining a prothrombotic state during coronary angiography.