The use of intravascular ultrasound (IVUS) guidance for drug-eluting stent (DES) optimization is limited by the number of adequately powered randomized control trials (RCTs). We performed an updated meta-analysis, including data from recently published RCTs and observational studies, by reviewing the literature in Medline and the Cochrane Library to identify studies that compared clinical outcomes between IVUS-guided and angiography-guided DES implantation from January 1995 to January 2016. This meta-analysis included 25 eligible studies, including 31,283 patients, of whom 3192 patients were enrolled in 7 RCTs. In an analysis of all 25 studies, the summary results for all the events analyzed were significantly in favor of IVUS-guided DES implantation [major adverse cardiac events (MACE, odds ratio [OR] 0.76, 95% confidence intervals [CI]: 0.70-0.82, P<0.001); death (OR 0.62, 95% CI: 0.54-0.72, P<0.001); myocardial infarction (OR 0.67, 95% CI: 0.56-0.80, P<0.001); stent thrombosis (OR 0.58, 95% CI: 0.47-0.73, P<0.001); target lesion revascularization (TLR, OR 0.77, 95% CI: 0.67-0.89, P=0.005); target vessel revascularization (TVR, OR 0.85, 95% CI: 0.76-0.95, P<0.001)]. However, in a separate analysis of RCTs, a favorable result for IVUS-guided DES implantation was found only for MACE (OR 0.66, 95% CI: 0.52-0.84, P=0.001), TLR (OR 0.61, 95% CI: 0.43-0.87, P=0.006), and TVR (OR 0.61, 95% CI: 0.41-0.90, P=0.013). IVUS-guided percutaneous coronary intervention was associated with better overall clinical outcomes than angiography-guided DES implantation. However, in a solely RCT meta-analysis, this benefit was mainly driven by reduced rates of revascularizations.