Arterial wall shear strain (WSS) has been proposed to impact the features of atherosclerotic plaques. The aim of this meta-analysis was to assess the impact of different types of WSS on plaque features in coronary artery disease (CAD). We systematically searched PubMed-Medline, EMBASE, Scopus, Google Scholar, and the Cochrane Central Registry, from 1989 up to January 2020 and selected clinical trials and observational studies which assessed the relationship between WSS, measured by intravascular ultrasound (IVUS), and plaque morphology in patients with CAD. In four studies, a total of 72 patients with 13,098 coronary artery segments were recruited, with mean age 57.5 � 9.5 years. The pooled analysis showed that low WSS was associated with larger baseline lumen area (WMD 2.55 [1.34 to 3.76, p < 0.001]), smaller plaque area (WMD −1.16 [−1.84 to −0.49, p = 0.0007]), lower plaque burden (WMD −12.7 [−21.4 to −4.01, p = 0.04]), and lower necrotic core area (WMD −0.32 [−0.78 to 0.14, p = 0.04]). Low WSS also had smaller fibrous area (WMD −0.79 [−1.88 to 0.30, p = 0.02]) and smaller fibro-fatty area (WMD −0.22 [−0.57 to 0.13, p = 0.02]), compared with high WSS, but the dense calcium score was similar between the two groups (WMD −0.17 [−0.47 to 0.13, p = 0.26]). No differences were found between intermediate and high WSS. High WSS is associated with signs of plaque instability such as higher necrotic core, higher calcium score, and higher plaque burden compared with low WSS. These findings highlight the role of IVUS in assessing plaque vulnerability.