Once a first interventional procedure has failed, patients with proximal left anterior descending in-stent restenosis are frequently sent for surgical revascularization. Data on long-term outcome in selected patients with proximal left anterior descending in-stent restenosis treated with RA are lacking. The study's objective was to evaluate the long-term outcome of patients with proximal left anterior descending artery in-stent restenosis treated with rotational atherectomy. The study population is constituted by 42 patients with proximal left anterior descending in-stent restenosis treated with rotational atherectomy. Patients were followed up for 2.1 +/- 0.9 years (range, 6--54). Restenosis length was 16.5 +/- 9.2 mm, and restenosis was diffuse (> 10 mm in length) in 30 (71.4%). The rotational atherectomy procedure was guided by intravascular ultrasound in 18 patients (42.9%). Maximum burr/artery ratio was > 0.7 in 24 (57.1%) patients. One patient suffered a periprocedural non--Q-wave infarction, but no deaths, Q-wave infarction, or new target vessel revascularization occurred during hospitalization. There were no deaths or myocardial infarctions after discharge. Sixteen patients (38.1%) needed a new revascularization, but only five (11.9%) underwent coronary bypass grafting at the end of the follow-up (2.1 +/- 0.9 years). The rate of surgical revascularization at 6 months, 1 year, and 3 years was 4.8%, 7.4%, and 18.4%, respectively. The rate of new target vessel revascularization at 6 months, 1 year, and 3 years was 16.7%, 36.5%, and 40.5%, respectively. Patients with < or = 5 months since stent implantation had a significantly higher rate of new target vessel revascularization. Patients with proximal left anterior descending in-stent restenosis may be safely treated with rotational atherectomy. This strategy is associated with a very good long-term outcome, with few patients undergoing surgical revascularization.