Objectives: We sought to evaluate the incidence and clinical impact of calcified nodule (CN) in patients with heavily calcified lesions requiring rotational atherectomy (RA). Background: It remains unclear whether CN impacts adversely on clinical outcomes in patients with heavily calcified lesions. Methods: Between January 2011 and February 2014, 264 patients after second-generation drug-eluting stent (DES) implantation following RA were retrospectively enrolled. CN was defined as a convex shape of the luminal side of calcium as assessed by intravascular ultrasound. The primary endpoint was the cumulative 5-year incidence of major adverse cardiac events (MACE), defined as a composite of cardiac death, clinically driven target lesion revascularization (CDTLR), and definite stent thrombosis (ST). Results: CN was observed in 128 patients (48.5%) with heavily calcified lesions. Cumulative 5-year incidence of MACE was significantly higher in the CN group than in the non-CN group, mainly driven by a higher rate of CDTLR and ST (35.4% vs. 18.8%, p <.001; 23.2% vs. 7.9%, p <.001; 7.0% vs. 0.93%, p =.009, respectively). Independent risk factors of 5-year MACE included hemodialysis (hazard ratio [HR] = 3.39, 95% confidence intervals [CI]: 2.00–5.73, p <.001), CN (HR = 2.53, 95% CI: 1.49–4.27, p <.001), ostial lesion (HR = 3.02, 95% CI: 1.58–5.78, p =.001), left ventricular ejection fraction ≤40% (HR = 2.17, 95% CI: 1.27–3.70, p =.005), and right coronary artery lesion (HR = 1.82, 95% CI: 1.07–3.11, p =.03). Conclusions: CN was observed in 48.5% of heavily calcified lesions, resulting in unfavorable long-term clinical outcomes after second-generation DES implantation following RA.