BACKGROUND: The additive effects of ezetimibe, evolocumab or alirocumab on lipid level, plaque volume, and plaque composition using intravascular ultrasound (IVUS) remain unclear. METHODS: According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, we performed a systematic review and meta-analysis of trials assessing the effects of ezetimibe, evolocumab, and alirocumab on coronary atherosclerosis using IVUS. The primary outcome was change in total atheroma volume (TAV), and the secondary outcomes were changes and differences in plaque composition and lipid content. RESULTS: Data were collected from 9 trials, involving 917 patients who received ezetimibe, evolocumab or alirocumab in addition to a statin and 919 patients who received statins alone. The pooled estimate demonstrated a significant reduction in TAV with the addition of ezetimibe and favorable effects of evolocumab and alirocumab on TAV. Subgroup analysis also supported favorable effects of evolocumab and alirocumab on TAV, according to baseline TAV, gender, type 2 diabetes mellitus, and prior stain use. Addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy resulted in significant reductions in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), but not in high-density lipoprotein cholesterol (HDL-C). The pooled estimate also showed significant favorable effects of ezetimibe on LDL-C, TC, and TG, but an insignificant effect on HDL-C. Patients who received ezetimibe showed similar changes in the necrotic core, fibro-fatty plaque, fibrous plaque, and dense calcification compared with patients not treated with ezetimibe. CONCLUSIONS: The addition of ezetimibe to statin therapy may further reduce plaque and lipid burdens but may not modify plaque composition. Although current evidence supports a similar impact from the addition of PCSK9 inhibitors to statin therapy, more evidence is needed to confirm such an effect.