This study evaluated the intermediate-term follow-up after excimer laser coronary angioplasty (ELCA) and adjunctive percutaneous transluminal coronary angioplasty (PTCA) in patients with diffuse in-stent restenosis (lesion length >10 mm). Clinical and angiographic follow-up were performed at 6 months. Quantitative coronary angiography performed at 3 stages-during stent implantation, before and after ELCA + PTCA, and at follow-up-included measurements of the minimum lumen diameter (MLD) and percent diameter stenosis (DS). Sixteen consecutive patients were included. The (median + range) stent length was 36 mm (range 15 to 105), with a restenotic lesion length of 32 mm (range 10 to 90). After ELCA + PTCA, the MLD increased from 0.60 +/- 0.41 to 2.28 +/- 0.50 mm, whereas the DS decreased from 76 +/- 16% to 22 +/- 8%. Despite adjunctive high-pressure PTCA, the MLD after ELCA + PTCA remained smaller than the MLD after initial stent implantation, (2.28 +/- 0. 50 mm vs 2.67 +/- 0.32 mm, p = 0.014). Adverse events included ELCA-related acute coronary occlusion in 4 patients and a per-procedural intracerebral hematoma in 1. At 6 months, there was recurrence of angina in all patients. Angiographic follow-up was completed in 13 patients (87%), showing a reocclusion in 6 (46%), a >50% DS in 6 (MLD 1.03 +/- 0.87 mm, DS 68 +/- 24%), and a distal de novo lesion in 1. Despite satisfactory acute angiographic results, the recurrence of significant restenosis in all patients suggests that ELCA + PTCA is not a suitable stand-alone therapy for diffuse in-stent restenosis of long stented segments.