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Based on single-center prospective registry data, the study evaluates short- and long-term results of intracoronary gamma radiation in patients with diffuse in-stent restenosis in the reality of routine clinical practice. Percutaneous coronary intervention and subsequent catheter-based irradiation with iridium-192 was performed in 84 vessels (81 patients) with diffuse in-stent restenosis. Repeat coronary angiography was performed in 35 patients with clinical restenosis. With a mean follow-up of 12.0 +/- 0.5 months, major adverse cardiac events were observed in 29 (34.5%) patients, including 2 cases of cardiac death, 3 myocardial infarctions, 21 target lesion revascularizations, and 4 target vessel revascularizations. Five of six patients with total occlusion of the target vessel at baseline developed target lesion restenosis. Late total occlusion of the target vessel was observed in four patients. The 1-year event-free survival rate was 69.8%. Total occlusion of the target vessel at baseline was the single independent predictor of cardiac events at 1-year follow-up (P < 0.001). In patients with a target lesion in the left anterior descending artery, predictors of cardiac events also included female sex (P = 0.014), current smoking (P = 0.014), stenting during brachytherapy session (P = 0.02), and smaller reference vessel diameter at baseline (P = 0.01). The results of our registry are similar to those of randomized trials. As applied in routine clinical practice, intracoronary gamma radiation is a feasible, safe, and effective tool in the treatment of diffuse in-stent restenosis. Late events in the entire group were predicted by total occlusion at baseline.