This prospective pilot study was designed to investigate the acute hemodynamic effects and clinical applicability of muscular counterpulsation (MCP), a one-shot procedure for biomechanical circulatory support. The study included 17 consecutive patients with coronary artery disease (CAD) and impaired ejection fraction (EF ≤45%) who underwent elective coronary artery bypass grafting (CABG). Patients were divided into control (n = 7) and treatment (n = 10) groups. MCP was applied through adhesive skin electrodes to the thighs and calves with a battery-powered, portable, ECG-triggered device for 15 minutes prior to general anesthesia. Standard ECG and invasive hemodynamic data were obtained from all patients. MCP was well tolerated in all patients, with no complications. Patients receiving MCP exhibited better cardiac function as indicated by reduced systemic vascular resistance and an augmented cardiac stroke index (+10%), which was maintained over time. After inducing general anesthesia via endotracheal intubation, the treatment group exhibited a reduced after-load (systemic vascular resistance index −28% and mean arterial pressure −10%) with increased left ventricular efficiency (stroke index/left ventricular stroke work index, +22%). Our findings indicate that MCP method was safe and easy to use in this patient population. In conclusion, a one-shot application of MCP prior to anesthesia was associated with an improvement in cardiac pump function and myocardial contractility.