Background Although both percutaneous transluminal coronary angioplasty (PTCA) and additional stenting can be used for the treatment for focal in-stent restenosis (ISR), no large-scale comparative data on the clinical outcomes after these interventional procedures have been reported. Methods In the current study we compared the in-hospital and long-term clinical results of PTCA alone (n = 266 patients, n = 364 lesions) versus stenting (n = 135 patients, n = 161 lesions) for the treatment of focal ISR, defined as a lesion length ≤10 mm. Results There were significantly more diabetic patients in the PTCA group than in the stent group (36% vs 26%, P = .04), but other baseline characteristics were similar. Lesion length and preprocedure minimal lumen diameter (MLD) were also similar in the two groups, but the stent group had a larger reference vessel diameter (3.40 ± 0.73 mm vs 2.99 ± 0.68 mm, P < .001). Stenting achieved a larger postprocedure MLD than PTCA did (2.95 ± 0.95 mm vs 2.23 ± 0.60 mm, P < .001) and a smaller residual diameter stenosis (11% ± 15% vs 23% ± 16%, P = .04). Angiographic success was achieved in all cases. The rate of death/Q-wave infarction of urgent revascularization was higher with PTCA than with stent (5.6% vs 0.7%, P = .02). Postprocedure creatine kinase myocardial band enzyme elevation >5 times normal was more frequent with stent (18.5% vs 9.7%, P = .05). At 1 year the two interventional strategies had similar cumulative mortality (4.6% PTCA vs 5.1% stent, P not significant) and target lesion revascularization rate (24.6% PTCA vs 26.5% stent, P not significant). By multivariate analysis, the sole predictor of target lesion revascularization was diabetes (odds ratio 2.4, 95% confidence intervals 1.2-4.7, P = .01). Conclusion Repeat stenting for the treatment of focal ISR had a higher postprocedure creatine kinase myocardial band elevation rate and similar long-term clinical results compared with PTCA alone. (Am Heart J 2001;141:610-4.)