Percutaneous rotational coronary atherectomy (PRCA) is commonly used in the percutaneous treatment of diffuse, calcified coronary lesions in stable coronary syndromes (SCSs) and facilitates successful delivery and deployment of balloons and stents. Early experience with PRCA cautioned its use in acute coronary syndromes (ACSs). However, the evolution of the PRCA technique and improved antiplatelet pharmacotherapy has broadened its use in ACSs also. A total of 1,112 consecutive patients with an ACS (n=269) or SCS (n=843) who underwent PRCA of 1,483 lesions were examined retrospectively to evaluate the angiographic and short-term clinical outcomes. Troponin-I was elevated in 33.3% of the ACS group and in 0.6% of the SCS group at baseline (p<0.001). Angiographic complications occurred more frequently in the ACS group (18.6% vs 13.1%, p=0.02). There was no difference in major complications between the groups (ACS 1.1% vs SCS 0.8%; p=0.44). The incidence of any periprocedural creatinine kinase-MB elevation was 17.1% versus 18.9% (p=NS) and 30-day major adverse cardiac events (death, disabling stroke, creatine kinase-MB >3 times the upper limit of normal, urgent revascularization) was 5.9% versus 4.6% (p=NS) when comparing the ACS and SCS groups, respectively. With current techniques and antiplatelet therapy, PRCA can be safely performed in ACSs when lesion morphology dictates, with outcomes comparable to that achieved in SCSs. Although angiographic complications occurred more frequently in the ACS group, this did not result in a significantly higher incidence of postprocedural myonecrosis or 30-day major adverse cardiac events.