Initial results, complications, restenosis rates and clinical outcomes were compared in 78 patients undergoing multilesion and 128 patients undergoing multivessel percutaneous transluminal coronary angioplasty (PTCA). Multilesion PTCA was defined as a procedure in which a proximal PTCA site had to be crossed to dilate a distal severe narrowing and multivessel PTCA as multiple dilatations without having to cross 1 severe narrowing to dilate another. The clinical and angiographic features of the 2 groups were similar. More sites per patient were attempted among those who underwent multilesion PTCA. Primary success rate per lesion was 86% (236 of 274) among those who underwent multivessel and 73% (155 of 211) among those who underwent multilesion PTCA (p less than 0.001). A success rate of 81% (101 of 124) for proximal lesions among those with multilesion PTCA was not significantly worse than that for those with multivessel PTCA; however, lesions distal to proximal sites had a success rate of only 62% (54 of 87), worse than either those with proximal stenoses or multivessel PTCA (p less than 0.005). Arterial diameter, severity of stenosis or procedural variables did not account for this difference. Complication rates were similar in the 2 groups. Despite a poorer success rate among patients with multilesion PTCA, clinical improvement to functional class 0 or 1 occurred in more than 70% of patients in both groups and was equal in patients with and without successful distal dilatations. Restenosis rates per lesion in patients with multivessel (31%) and multilesion (30%) PTCA were similar.(ABSTRACT TRUNCATED AT 250 WORDS)