To determine the influence of a history of restenosis on subsequent restenosis after percutaneous transluminal coronary angioplasty (PTCA) of a new significant narrowing, the records of 100 patients who underwent successful PTCA at another site ("new narrowing PTCA") greater than or equal to 2 months after successful initial PTCA were retrospectively reviewed. Patients were grouped according to whether initial PTCA resulted in restenosis, which was determined by angiographic follow-up greater than or equal to 3 months after initial PTCA. Patients in group 1 did not have restenosis after initial PTCA (n = 50), whereas patients in group 2 did (n = 40). All patients were followed for recurrent symptoms, with serial exercise tests, for greater than or equal to 6 months after new narrowing PTCA. Clinically suspected and angiographically confirmed restenosis occurred in 11 of 50 (22%) patients and 12 of 63 (19%) narrowings in group 1, and in 20 of 40 (50%) patients and 22 of 48 (46%) narrowings in group 2 (p less than 0.01 for patients, p less than 0.002 for narrowings). Multivariate analysis identified that prior restenosis (p less than 0.02, odds ratio 3.4), left anterior descending artery location of stenosis (p less than 0.04, odds ratio 3.0), and severity of stenosis before PTCA (p less than 0.02, odds ratio 1.8) were independently associated with restenosis after new narrowing PTCA. In conclusion, prior restenosis is an independent risk factor for subsequent restenosis after new narrowing PTCA.