Abstract Introduction Several pioneering studies have reported that continuous administration of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor reduces cardiovascular events and plaque volume on intravascular ultrasound and increase the thickness of the fibrous-cap on optical coherence tomography after 52-76 weeks.[1,2] However, the effect of PCSK9 inhibitors in very short period of time has not adequately been evaluated. Purpose This study aimed to investigate the effect of the single dose of PCSK9 inhibitor in regard to serial change of plaque composition in very short period with near-infrared spectroscopy with intravascular ultrasound (NIRS-IVUS). Methods This prospective, single arm, single-center, interventional study included 27 consecutive coronary artery disease patients (silent myocardial ischemia and stable angina) who performed NIRS-IVUS at the time of coronary angiography for diagnosis between June 2021 and August 2023. Maximal lipid-core burden index over any 4-mm segment (max-LCBI4mm) and total lipid-core burden index (T-LCBI) at the target lesions were assessed with NIRS-IVUS and they were administered evolocumab 420mg. After 2 to 6 weeks, percutaneous coronary intervention (PCI) was performed on a standby basis and repeat NIRS-IVUS were performed at PCI. Results The median max-LCBI4mm showed a significant decrease from 387 to 315 (IQR: 268 to 572 and IQR: 221 to 488, respectively; p = 0.02) in a lesion-wise analysis. The median T-LCBI also showed a significant decrease from 160 to 117 (IQR: 105 to 263 and IQR: 65 to 226, respectively; p = 0.02). Minimum lumen area and minimum lumen diameter showed no significant changes. Conclusions Single dose of PCSK9 inhibitor therapy before PCI resulted in significant degression of lipid core plaques identified by NIRS at the target lesion in very short period of time.Changes of max-LCBI4mmChanges of T-LCBI