Background: Coronary calcifications, particularly in left main disease (LMD), are independently associated with adverse outcomes of percutaneous coronary intervention (PCI). Adequate lesion preparation is pivotal to achieve favorable short- and long-term outcomes. Rotational atherectomy devices have been used in contemporary practice to obtain adequate preparation of the calcified lesions. Recently, novel orbital atherectomy (OA) devices have been introduced to clinical practice to facilitate the preparation of the lesion. The objective of this study is to compare the short-term safety and efficacy of orbital and rotational atherectomy for LMD. Methods: we retrospectively evaluated a total of 55 consecutive patients who underwent the LM PCI supported by either OA or RA. Results: The OA group consisted of 25 patients with a median SYNTAX Score of 28 (26–36). The Rota group consisted of 30 patients with a median SYNTAX Score of 28 (26–33.1) There were no statistical differences in MACCE between the RA and OA subpopulations when recorded in-hospital (6.7% vs. 10.3%p= 0.619) as well as in a 1-month follow-up after the procedure (12% vs. 16.6%p= 0.261). Conclusion: OA and RA seem to be similarly safe and effective strategies for preparating the lesion in the high-risk population with calcified LMD.