OBJECTIVE--To report on the short-term and long-term results of patients who underwent a third coronary balloon angioplasty for a second restenosis and to identify the correlates of a third clinical restenosis. DESIGN--A retrospective analysis of clinical, angiographic, and procedure related variables of a consecutive series of patients. PATIENTS--62 patients (mean (range) age 53 (31-72) years; 84% men) who underwent a third coronary balloon angioplasty of a single coronary artery segment at which restenosis had occurred after two previous angioplasty procedures between 1986 and 1992. RESULTS--Procedure success was achieved in 56 patients (90%). Complications included one myocardial infarction (2%) and one emergency coronary artery bypass surgery (2%). Complete follow up data were available (median (range) 48 (12-94) months). During the follow up period, four patients (6%) died, two (3%) had a non-fatal myocardial infarction, and five (8%) underwent elective coronary artery bypass surgery. Nine patients (14%) underwent a fourth angioplasty for a third clinical restenosis, and three (5%) had a fourth angioplasty procedure for new coronary lesions. The cumulative probability of survival for all 62 patients was 97% and 95% at 1 and 5 years, respectively. The 1 and 5 year freedom from death, infarction, bypass surgery, and repeat angioplasty was 82% and 66.6%, respectively. At census, of the 58 survivors, 31 (53%) were asymptomatic and only eight (14%) complained of angina grade III or IV (P < 0.001). A third clinical restenosis occurred in 22 (39%) of the 56 patients who had initially successful procedures. Multiple stepwise logistic regression analysis identified the interval between the second and third angioplasty procedure as the only independent predictor of a third clinical restenosis (P = 0.004). CONCLUSIONS--A third coronary angioplasty for a second restenosis can be performed safely and effectively and should be considered as an integral part of the overall coronary angioplasty revascularisation strategy. The incidence of a third clinical restenosis remains high, however, and is correlated with the interval between the previous angioplasty procedures.