The incidence of major complications associated with nonionic contrast media has not been defined in a large study. Accordingly, cardiovascular complications, especially thrombotic events, were prospectively evaluated in 8,517 consecutive patients undergoing diagnostic cardiac catheterization with either iopamidol (n = 6,293) or iohexol (n = 2,224). Thrombotic events were defined as coronary embolus, coronary occlusion, transient ischemic attack or stroke occurring at the time of catheterization. Thrombotic events occurred in 15 patients (0.18%). Coronary thrombus or embolus occurred in 7 patients, a thromboembolus from the ventricular catheter occurred in 1 patients and transient ischemic attack or stroke occurred in 7 patients. Six of 15 patients with thrombotic events were premedicated with heparin. Thrombotic events were unusual in that they tended to occur in clusters within short time intervals. On 1 occasion, a thrombus was observed in the catheter tip before embolization. Other cardiovascular complications were similarly low with an incidence of ventricular tachycardia/fibrillation of 0.1%, profound bradycardia of 0.2% and prolonged angina of 0.3%. There were 2 deaths unrelated to thrombotic events. Although the clinical thrombotic events associated with nonionic contrast have an unusual temporal clustering and may result in major complications, the overall incidence (0.18%) of these thrombotic complications with nonionic contrast agents is quite similar to that reported with ionic contrast media.