An increasing body of evidence suggests that the potential for thrombotic complications is greater with nonionic than with ionic contrast agents. This is a particularly important consideration in the highly thrombogenic setting of percutaneous transluminal coronary angioplasty (PTCA). To explore this issue further, 500 consecutive patients undergoing PTCA were prospectively randomized to receive the low osmolality ionic ioxaglate or the nonionic agent iohexol. The number of acute thrombotic in-laboratory events was significantly less in the ioxaglate than in the iohexol group (8 versus 18; P < 0.05), but there was no significant difference between the 2 groups as regards the number of out-of-laboratory acute rethrombotic events. With multivariate analysis, use of the nonionic agent rather than the ionic agent emerged as an independent predictor of acute in-laboratory rethrombosis. These data suggest that, in the performance of PTCA, an ionic, rather than a nonionic, should be the preferred contrast agent.