In-stent restenosis (ISR), when treated with balloon angioplasty (PTCA) alone, has an angiographic recurrence rate of 30-85%. Ablating the hypertrophic neointimal tissue prior to PTCA is an attractive alternative, however late outcomes of such treatment have not been fully determined. This multicenter case control study assessed angiographic and clinical outcomes of 137 consecutive procedures in 125 patients treated for ISR with either PTCA alone (n=58) or excimer laser assisted coronary angioplasty (ELCA, n=67). Demographics were similar. Lesions selected for ELCA compared with those selected for \PTCA were longer (17.1+/-9.9 mm vs. 13.6+/-9.1 mm; p=0,034), more complex (ACC/AHA type C: 36,5% vs. 14,3%; p=0,006), and with reduced antegrade flow (TIMI flow <3: 18,9% vs. 4,8%; p=0,025). IELCA- and PTCA treated patients had similar rates of procedural success (98,5 and 98,3%, respectively, p=1,0), major clinical complications (3,0% and 8,6%; respectively, NS), major cardiac events at 1 year (37,3 and 46,6%. respectively, ISIS), and target lesion revascularization (32,8 and. 34,5%; respectively, NS). These data suggest that ELCA in patients with complex in-stent restenosis is as safe and effective as PTCA. Despite higher lesion complexity in ELCA-treated patients, no increase in event rates was observed.