An in vitro study was done to investigate the thrombogenic potential of nonionic contrast media. Whole blood from 18 healthy volunteers was mixed with ionic contrast medium (diatrizoate, ioxaglate), a non-ionic contrast medium (iohexol), or saline (the control) and incubated in glass and plastic test tubes. Levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), and antithrombin III (AT III) were measured. Evidence showed increased thrombin formation in glass tubes compared with that in plastic tubes, a finding in concordance with the known association between contact with glass and increased activation of coagulation. F1 + 2 and TAT levels were significantly increased in the nonionic mixtures compared with such levels in ionic mixtures (P less than or equal to .05). Control mixtures showed little or no overall increased thrombin formation by F1 + 2 and TAT levels compared with nonionic mixtures. These findings suggest an inhibition of thrombin generation by ionic contrast media in vitro and a relative lack of such inhibition by iohexol.