We randomized 800 patients in a prospective study comparing the angiographic results, device usage and in-hospital outcome of balloon angioplasty of primary stenoses of native coronary vessels with low-compliant and highly compliant balloons. The cumulative incidence of prespecified clinical endpoints was 8.0% in both treatment groups. The primary angiographic success rates were 83.9% and 78.9% in the high- and low-compliance group, respectively (P = 0.05). For the lesions dilated with one study balloon only, the quantitative angiographic findings were virtually identical in the two treatment groups. The total number of dissections was slightly but not significantly higher in the lesions treated with a highly compliant balloon. The global usage of angioplasty balloons was similar in both treatment groups. We conclude that, in general, there is no objective reason to prefer one balloon material to another on the basis of its compliance characteristics.