Treatment of in-stent restenosis (ISR) with conventional PTCA causes significant recurrent neointimal tissue growth in 30-85% of the cases. Therefore, laser ablation of intra-stent neointimal hyperplasia prior to balloon dilatation 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 prior to balloon dilatation 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 mm versus 13.6±9.1 mm; p=0.034), more complex (36.5% type-C stenoses versus 14.3%; p=0.006) and more frequently had reduced distal blood flow (TIMI < 3: 18.9% versus 4.8%; p=0.025) compared to lesions in 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 versus 8.6% in PTCA group). The 1 year-follow-up showed that the rates of MACE were comparable in the two groups (37.3% in ELCA group versus 46.6% in PTCA group). The rates of TVR within 1 year after the intervention were also similar in ELCA and PTCA groups (32.8% versus 34.5%). The data mean that ELCA in patients with complex ISR is efficient and safe. Despite a higher complexity of lesions in ELCA group, no increase in the rate of complications was registered.