High-speed rotational atherectomy (HSRA) is advocated for calcified and diffusely narrowed coronary arteries. There are often side branches involving these kinds of lesions. The presence of significant lesion-related side branches has been considered a relative contraindication to rotational atherectomy. This study was performed to determine the rate, predictors, and outcome of side branch occlusion after HSRA. The angiograms of 418 patients were examined with 320 side branches in 240 target vessels of > or = 1 mm in diameter being identified. Vessels were scored as either perfused (Thrombolysis In Myocardial Infarction 2 or 3 flow) or occluded (Thrombolysis In Myocardial Infarction 0 or 1 flow before and after the procedure. A detailed quantitative angiographic analysis was performed on a total of 108 side branches including all cases of branch occlusion. Clinical outcomes were determined in all cases with side branch loss. There were 24 occlusions in 21 patients after the procedure, giving a rate of branch loss of 7.5%. Follow-up angiography of > or = 24 hours was available for 13 of the occluded branches and 12 were found to be patent. In the 21 patients with branch occlusion, 6 sustained a myocardial infarct (of which 5 were non-Q-wave), 2 underwent coronary artery bypass grafting, and 2 died. There are frequently lesion-associated side branches in the types of vessels to undergo HSRA. These branches remained patent 92.5% of the time, with occlusion occurring infrequently and usually being transient. When occlusion did occur, there was a 29% incidence of myocardial infarction.