Nonionic radiographic contrast media are used frequently in diagnostic and interventional angiography. However, there is concern that they may possess thrombogenic properties, and some studies have suggested that patients receiving nonionic contrast media are difficult to systemically anticoagulate with intravenous heparin. To investigate the potential effects of nonionic contrast media on systemic anticoagulation during diagnostic cardiac catheterization, pharmacokinetics and in vitro anticoagulant activity following a 3,000 U intravenous heparin bolus were assessed in 12 patients assigned randomly to either an ionic or a nonionic contrast agent. Independent of contrast agent, all patients exhibited biphasic (nonlinear) heparin pharmacokinetics characterized by an initial rapid disappearance phase, followed by a second slower phase. Each patient achieved a therapeutic plasma heparin concentration ( ≧ 0.2 U/ml) within 10 min of receiving the bolus, and maintained this level throughout the procedure. Heparin anticoagulant activity, as estimated by a standard activated partial thromboplastin time (APTT) was not affected differently by nonionic as compared with ionic contrast media (p > 0.05). Each patient rapidly achieved a level of systemic anticoagulation commonly considered therapeutic (APTT ≧ 1.5 times the control), and maintained this level throughout the procedure. In both groups, APTT correlated directly with plasma heparin concentration (r = 0.95; p < 0.0001), and inversely with the total amount of contrast media used during the procedure (r = -0.25; p = 0.01). Plasma heparin concentration did not correlate with total contrast media (r = -0.16; p > 0.05). In conclusion, among low-risk patients undergoing diagnostic coronary angiography, heparin pharmacokinetics and in vitro anticoagulant activity are not influenced differently by the use of nonionic as compared with ionic radiographic contrast media.