The non-ionic contrast medium iopentol (Imagopaque, Nycomed Imaging AS, Oslo, Norway) 350 mg I/ml was compared for safety and efficacy with the ionic contrast medium diatrizoate (Urografin, Schering AG, Berlin, Germany) 370 mg I/ml in a randomized, double-blind, parallel-group clinical trial in cerebral computed tomography (CT). The numbers of participating patients was 79; forty in the iopentol group and 39 in the diatrizoate group. Safety was evaluated by assessing the numbers of patients reporting immediate adverse events (up to 30 min after injection) and delayed adverse events (within 7 days after the examination). Efficacy was expressed as the quality of visualization of the cerebral lesions after injection of the contrast medium. In addition, Hounsfield units were measured pre- and post-contrast. No patient in either group experienced any serious adverse event. The frequency of patients with immediate adverse events was statistically significantly lower in the iopentol group (23%) than in the diatrizoate group (64%), p = 0.0003. Delayed adverse events were also significantly less frequent in the iopentol group (43%) than in the diatrizoate group (69%), p = 0.047. Patients in the iopentol group reported significantly less discomfort (53%), especially sensation of warmth, than patients in the diatrizoate group (92%), p = 0.0001. The intensity of adverse events and injection-associated discomfort seemed, in general, to be lower for patients in the iopentol group. No difference was found between the two contrast media regarding efficacy.