Background Rotational atherectomy (RA) is relatively contraindicated in patients with lesions ≥25 mm of length. Aim of this study was to evaluate RA safety and efficacy in this subset of patients with new technology and devices. Methods and Results From April 2002 to August 2013, the ROTATE registry included all consecutive patients undergoing RA in 8 centres. They were divided into shorter lesion group (SLG, lesions < 25 mm) and longer lesion group (LLG, lesions ≥ 25 mm). The angiographic success (AS) was the primary end point. Procedural complications (PC), a composite end point of procedural perforation, slow flow/no flow, and in‐hospital major acute cardiovascular events (MACE), were secondary end points, along with death, nonfatal MI, target lesion revascularization, and MACE during follow‐up. Sensitivity analysis was performed according to generation of DES. 1186 patients were included: 51.5% in SLG and 48.4% in LLG. Mean age was 70.4 ± 9.3 years, 64.5% were male. AS and PC did not differ between the two groups (93% vs 91%, p = 0.24 and 9.8 vs 9.4%, p = 0.84). During follow‐up (27.6 ± 22.9 months), MACE did not differ between the two groups (28% vs 29.1%, p = 0.95). At multivariate analysis chronic kidney disease, male gender increased risk of MACE (HR 1.94, IQR 1.29–2.0, p = 0.01, HR 0.52, IQR 0.34–0.79, p = 0.01) while second‐generation DES seemed protective (HR 0.53, IQR 0.31–0.88, p = 0.02). Data were confirmed at sensitivity analysis for second‐generation DES (759 pts, 63.9%). No differences were found in this subpopulation between the two groups in term of AS, PC, and long‐term MACE (93.6% vs 93.5%, p = 0.28, 11.9% vs 9.4%, p = 0.32 and 25.5% vs 23.9%, p = 0.72, respectively). Conclusions Treating coronary lesions ≥ 25 mm length with RA does not impact short‐ and long‐term outcome, in particular, in patients with second‐generation DES. © 2016 Wiley Periodicals, Inc.