Treatment of in-stent restenosis (ISR) with conventional percutaneous transluminal coronary angioplasty (PTCA) causes significant recurrent neointimal tissue growth in 30-85%. Therefore, laser ablation of intrastent neointimal hyperplasia before balloon dilation can be an attractive alternative. However, the long-term outcomes of such treatment have not been studied thoroughly enough. This prospective case-control study evaluated angiographic and clinical outcomes of PTCA alone and a combination of excimer laser coronary angioplasty (ELCA) and adjunct PTCA in 125 patients with ISR. ELCA was performed before balloon dilation in 67 patients, PTCA alone was performed in 58 patients. Basic demographic and clinical data were comparable in both groups. Lesions included in ELCA group were longer (17.1 +/- 9.9 vs 13.6 +/- 9.1 mm; p = 0.034), more complex (36.5% type C stenoses vs 14.3%; p = 0.006), and more frequently had reduced distal blood flow (TIMI < 3: 18.9% vs 4.8%; p=0.025) compared to lesions in the PTCA group. Immediate angiographic results of PTCA and ELCA + PTCA appeared to be comparable. PTCA alone was successful in 57 patients (98.3%), ELCA + PTCA, in 66 patients (98.5%). The rates of hospital complications were comparable (3.0% in ELCA group vs 8.6% in PTCA group). The 1-year follow-up showed that the rates of major adverse cardiac events (MACE) were comparable in the 2 groups (37.3% in ELCA group vs 46.6% in PTCA group). The rates of target vessel revascularization (TVR) within 1 year after the intervention were also similar in the 2 groups (32.8% vs 34.5%). The data mean that ELCA in patients with complex ISR is efficient and safe. Despite a higher complexity of lesions in the ELCA group, no increase in the rate of complications was registered.