<p>Rotational atherectomy (RA) is an effective, mature, and specific treatment for calcified lesions. However, the incidence of RA-related myocardial injury remains high and has not been adequately addressed. To assess the safety and efficacy of low-temperature RA-flush solution versus room-temperature RA-flush solution during RA. A total of 132 patients with moderate-to-severe calcified lesions who underwent RA were randomly assigned to the low-temperature RA-flush solution group or the room-temperature RA-flush solution group. The primary endpoint was RA-related myocardial injury, defined as any increase in myocardial biomarkers within 72&#xa0;h after percutaneous coronary intervention (PCI). Secondary endpoints included RA-related myocardial infarction (MI), RA-related transient slow/no flow, or transient coronary spasm. A total of 78 patients (59.1%) had increased cardiac troponin I (cTnI) levels, and 60 patients (45.5%) had increased creatine kinase isoenzyme (CK-MB) levels after PCI. The number of patients with myocardial injury (primary endpoint), defined as elevated cTnI (47.0% vs. 71.2%, <i>p</i> = 0.005) or elevated CK-MB (28.8% vs. 62.1%, <i>p</i> &lt; 0.001), was significantly lower in the low temperature group than in the room temperature group. The number of patients with RA-related transient slow/no flow (6.1% vs. 34.8%, <i>p</i> &lt; 0.001) and transient coronary spasm (9.1% vs. 25.8%, <i>p</i> = 0.012) (secondary endpoints) was significantly lower in the low temperature group than in the room temperature group; no significant difference in the incidence of RA-related MI was observed between the two groups. Compared with room-temperature RA-flush solution, low-temperature RA-flush solution is associated with reduced RA-related myocardial injury in patients treated with RA.</p><p>Registration: URL: <a href="https://www.clinicaltrials.gov">https://www.clinicaltrials.gov</a>; Unique identifier: NCT03701230; first submitted registration date: 09/10/2018.</p>