While rotational atherectomy (RA) is used for complex lesions in percutaneous coronary intervention, there are several contraindications such as unprotected left main stenosis or left ventricular dysfunction. We previously reported that the incidence of in-hospital complications was significantly greater in off-label as compared to on-label use RA. However, the mid-term clinical outcomes between off-label and on-label RA have not been investigated. The purpose of this study was to compare the mid-term clinical outcomes between off-label (n = 156) and on-label RA (n = 94). The primary endpoint was the incidence of major adverse cardiovascular events (MACE) defined as the composite of ischemia-driven target vessel revascularization (TVR), non-fatal MI, and all-cause death. We also identified 154 patients who underwent RA and follow-up angiography within 1 year, and compared quantitative coronary analysis between the off-label group (n = 96) and on-label group (n = 58). There was no significant difference in late luminal loss between the groups (0.03 ± 0.53 mm in the off-label and −0.05 ± 0.44 mm in the on-label groups, P = 0.57). However, the incidence of MACE was less in the on-label group (3.2 %) as compared to the off-label group (9.0 %) without reaching statistical significance (P = 0.08). In conclusion, mid-term clinical outcomes tended to be worse in the off-label group than in the on-label group. We may have to follow-up the patient who underwent off-label RA more carefully than the patient who underwent on-label RA.