Background: Although several meta-analyses have demonstrated the utility of intravascular ultrasound (IVUS) in guiding drug-eluting stent (DES) implantation compared to angiography-guidance, there has been a dearth of evidence in the left main coronary artery (LMCA) lesion subset. Methods: We performed a meta-analysis to compare clinical outcomes of IVUS versus conventional angiography guidance during implantation of DES for patients with LMCA disease. Pubmed, Cochrane Library, Embase were searched. Results: A total of 1002 publications were reviewed; and finally, seven clinical studies - one prospective randomized controlled trial and six observational studies with 4592 patients (1907 IVUS-guided and 2685 angiography-guided) were included in the meta-analysis. IVUS guidance was associated with a significant reduction in major adverse cardiac events (relative ratio [RR] 95% Cl 0.61; 95% confidence interval [Cl] 0.53 to 0.70; P < 0.001), all-cause death (RR 0.55; 95% Cl 0.42 to 0.71; P < 0.001), cardiac death (RR 0.45; 95% Cl 0.32 to 0.62; P < 0.001), myocardial infarction (RR 0.66; 95% Cl 0.55 to 0.80; P < 0.001), and stent thrombosis (RR 0.48; 95% Cl 0.27 to 0.84; P = 0.01) compared with angiographic guidance. However, there was no significant difference regarding target lesion revascularization (RR 0.60; 95% Cl 0.31 to 1.18; P = 0.099) and target vessel revascularization (RR 0.64; 95% Cl 0.26 to 1.56; P = 0. 322). Conclusions: Compared to angiographic guidance, IVUS-guided DES implantation was associated with better clinical outcomes for patients with LMCA lesions, especially hard endpoints of death, myocardial infarction, and stent thrombosis.