Aim of this randomized, double-blind, parallel group study was to compare the safety, tolerance and diagnostic efficacy of iomeprol and iopamidol, both at iodine concentration of 150 mgI/ml, in 100 adult patients undergoing peripheral intra-arterial digital subtraction angiography (IA-DSA). All patients underwent extensive pre- and post-contrast clinical, instrumental and laboratory evaluation for safety assessments. The tolerance to the test compounds was evaluated in terms of discomfort associated with the injection of the test compounds. Image quality was prospectively graded by two independent readers according to a five-point scale as 1, insufficient; 2, sufficient; 3, good; 4, excellent; or E, excessive. At the end of the study, two experienced radiologists working at institutions other than the study centre and not aware of patients identity, clinical profile or results of other imaging procedures, jointly evaluated study images using the same ordinal scale. The procedure was always well tolerated. None of the studied patients experienced adverse events. All angiographic examinations were rated as diagnostic. The quality of the radiographs was judged as excellent or good in most individual patient studies, without significant differences between the two study groups. No significant differences between the results of prospective on-site assessment and retrospective external assessment were detected. The results of our study show that iomeprol and iopamidol are equally effective, well tolerated and safe contrast agents when used for peripheral IA-DSA.