PURPOSE: Long lesions remain a challenging task in interventional cardiology, with a high propensity of restenosis, especially within the stented segment. Although intracoronary gamma-radiation has been proved to reduce diffuse in-stent restenosis in long lesions, such an effect remains to be determined using beta-radiation. METHODS AND MATERIALS: Of 1098 consecutive patients at 46 European centers treated with localized beta-radiation ((90)Sr, Novoste Beta-Cath System), 139 patients (mean age 61.5 +/- 10.7 years, 84% male, 22% with diabetes mellitus) with lesions treated using a >40-mm source length underwent radiation using a single 60-mm source train (34%) or a stepping/pullback procedure with a 30-mm (12%) or 40-mm (87%) source length after conventional interventional procedures. The mean lesion length was 35.3 +/- 17.9 mm. RESULTS: Technical success was achieved in 96% of cases. Geographic miss was noted in 9 patients (6.5%). The reference (placebo) group was obtained from the Washington Hospital Center for In-Stent Restenosis Trial (WRIST) and the WRIST Trial for long lesions (LONG WRIST) studies by selecting the cases (94 patients) that required a dummy source length >/=13 seeds (or >51 mm in length). Statistically significant improvement was noted in late angiographic restenosis (34.7% vs. 76.5%, p <0.0001), target vessel revascularization (14.9% vs. 60.6), and major adverse cardiac events (i.e., death, myocardial infarction, or total vessel revascularization) (17.9% vs. 64.9%, p <0.0001) at 6 months in reference to the nonradiation group. CONCLUSION: This subanalysis from the Radiation in Europe with Novoste study confirms the safety and efficacy of beta-radiation combined with conventional interventional procedures in patients with diffuse, long, in-stent restenosis