Intravascular ultrasound (IVUS) guidance is not routinely performed in real-word clinical practice partly because the benefit of IVUS guidance is not well established. This updated meta-analysis aims to compare IVUS-guided and angiography-guided drug-eluting stent (DES) implantation, simultaneously stressing the value of an optimal IVUS-defined procedure. Medline, Scopus, Google Scholar, and Cochrane Controlled Trials Registry were searched for the randomized trials comparing IVUS-guided and angiography-guided DES implantation. Nine eligible randomized trials including 4,724 patients were identified. At a mean follow-up of 16.7 months, IVUS guidance was associated with a significant lower risk of major adverse cardiovascular events (MACE) [5.4% vs. 9.0%; relative risks (RR): 0.61, 95% confident interval (CI) 0.49–0.74, p < 0.001], cardiac death (0.6% vs. 1.2%; RR: 0.49, 95% CI 0.26–0.92, p = 0.03), target vessel revascularization (3.5% vs .6.1%; RR: 0.58, 95% CI 0.42–0.80, p = 0.001), target lesion revascularization (3.1% vs. 5.2%; RR: 0.59, 95% CI 0.44–0.80, p = 0.001), and definite/probable stent thrombosis (0.5% vs .1.1%; RR: 0.45, 95% CI 0.23–0.87, p = 0.02) compared with angiography guidance. No significant differences in all cause death and myocardial infarction were noted between the two groups. Subgroup analysis showed that patients who met the optimal criteria had a lower rate of MACE than those with IVUS-defined suboptimal procedure (RR: 0.33, 95% CI 0.06–0.60, p = 0.02). The present meta-analysis with the largest sample size to date demonstrates that IVUS-guided DES implantation significantly reduces cardiac death, coronary revascularization and stent thrombosis, particularly for patients with IVUS-defined optimal procedures compared with angiography guidance.