Background In open-chest coronary artery bypass grafting (CABG), the surgeon faces several intraoperative challenges: (1) to locate the target coronary artery, (2) to select the optimal anastomotic site, and (3) to assess the quality of the graft and distal anastomosis. Endoscopically, these three diagnostic aims are particularly challenging. Methods We reviewed the literature on the intraoperative application of high-frequency (6.5-15 MHz) epicardial ultrasound (ECUS) in CABG to aid in these challenges. Results Overall, ECUS was used in 628 patients to visualize and assess 912 (segments of) coronary arteries, as well as 418 grafts and distal anastomoses. In 96 cases, ECUS successfully located a coronary artery that was buried in the epicardial and/or myocardial tissue. In 37/155 (24%) imaged anastomotic sites, an alternative site free of pathology was selected. For quality assessment of the coronary anastomosis, experimental validation of ECUS included 218 anastomoses in ex vivo and animal models. ECUS showed high sensitivity (0.98) and specificity (1.00) for detection of anastomotic construction errors in 120 ex vivo anastomoses. In 418 grafts and distal anastomoses evaluated in patients, irregularities leading to revision were detected in 8 (1.9%) anastomoses and minor irregularities in an additional 23 (5.5%) anastomoses. However, little is known about the effect on long-term patency of specific anastomotic abnormalities revealed by ECUS. Scanning of arteries and anastomoses required several minutes. Current size ultrasound probes allowed successful experimental robot-assisted endoscopic application of ECUS. Conclusions CABG may be facilitated and improved in several ways by intraoperative high-frequency epicardial ultrasound scanning. Totally endoscopic CABG may benefit from ultrasound diagnostics in particular.