<h3>Objective</h3> Non-invasive echocardiographic analysis of left ventricular (LV) myocardial work (MW) enables insights into cardiac mechanics, contractility, and efficacy beyond ejection fraction and global longitudinal strain. MW incorporates myocardial deformation and loading conditions into its analysis and correlates well with invasively measured myocardial work outside the operative setting. However, there are no reports on the use of this method by transesophageal echocardiography (TEE) in patients undergoing coronary artery bypass graft (CABG) surgery. Therefore, we aim to describe the intraoperative course of this novel assessment tool of ventricular function in these patients and compare it to conventional two- and three-dimensional echocardiographic parameters and strain analysis. <h3>Design and Method</h3> Twenty-five patients scheduled for isolated on-pump CABG surgery with preoperative preserved left and right ventricular function and a complication-free intraoperative course, were included into this prospective observational trial. TEE was performed intraoperatively after induction of anesthesia (T1), after termination of cardiopulmonary bypass (T2), and after sternal closure (T3) using General Electric Vivid E95 echocardiography machines and 6VT-D TEE probes. All measurements were performed under stable hemodynamic conditions, in sinus rhythm or atrial pacing and vasopressor support with Norepinephrine ≤ 0.1 µg/kg/min. EchoPAC v204 software (GE Vingmed Ultrasound AS, Norway) was used for analysis of 2D- and 3D LV ejection fraction (EF), LV global longitudinal strain (GLS), LV global work index (GWI), LV global constructive work (GCW), LV global wasted work (GWW) and LV global work efficiency (GWE). <h3>Results</h3> Myocardial work analysis was feasible in all patients. Although there was no significant difference in the values of 2D- and 3D-EF during the intraoperative interval, GLS deteriorated significantly after CABG compared to assessment after induction of anesthesia (T1 v T2, -13.3±3.0% v -11.6±3.1%; p=0.012). GWI declined significantly after surgery (T1 v T2, 1224±312mmHg% v 940±267mmHg%; p<0.001) as well as GCW (T1 v T2, 1460±312mmHg% v 1244±336 mmHg%; p=0.005). GWW increased after CABG (T1 v T2, 143mmHg% (IQR 99-183) v 251mmHg% (IQR 179-361); p<0.001) and GWE decreased (T1 v T2, 89% (IQR 85-92) v 80% (IQR 75-87); p<0.001). There was no significant change in the values of 2D- and 3D-EF, GLS, GWI, GCW, GWW and GWE before and after sternal closure (T2 v T3). <h3>Conclusions</h3> Intraoperative non-invasive echocardiographic assessed left ventricular myocardial work analysis appears feasible in this study. In our small sample with 25 CABG patients, strain and myocardial work analysis showed a deterioration of left ventricular function. In the short-term period after uncomplicated on-pump CABG, global and constructive myocardial work was decreased, while wasted work was increased, resulting in a less efficient left ventricle. None of these aspects was detected by two- and three-dimensional ejection fraction. Therefore, myocardial work analysis might be a more sensitive parameter in detecting myocardial dysfunction by TEE in the perioperative setting.