Abstract Rotational atherectomy (RA) is a minimally invasive procedure to remove the calcified atherosclerotic plaque from arteries to restore blood flow. It uses a high-speed, metal-bonded diamond abrasive grinding wheel to pulverize the calcified plaque into absorbable debris via a catheter through the artery. Although RA has been clinically used for over two decades, procedural complications persist and there remains a lack of consensus on the optimal device parameters. This study aims to investigate the material removal rate (MRR) in coronary RA with respect to grinding wheel sizes and rotational speeds based on a tissue-mimicking phantom. Three grinding wheel sizes, 1.25, 1.5, and 1.75 mm in diameter, and three rotational speeds, 1,20,000, 1,50,000, and 1,80,000 rpm, were investigated. The RA MRR was presented as the luminal area gain and measured by microscopy and image processing. The results show the increase in the grinding wheel size or rotational speed leads to a higher MRR and luminal gain in RA. With a 1.75 mm diameter grinding wheel rotating at 1,80,000 rpm in a 2 mm initial diameter lumen, the max MRR and the luminal gain are 2.49 mm2/three passes and 5.09 mm2, respectively. The MRR decreases as the number of grinding passes increases during RA with the same grinding wheel rotating at a constant speed. This study provides a thorough understanding of the wheel size and speed effects on coronary RA MRR for potential improvements in RA devices and clinical operational guidelines.