Background: The aim of this prospective study was to compare continuous cardiac output measurements of the non-invasive cardiac output system (NICO) with the pulmonary artery catheter during off-pump coronary bypass surgery. Methods: Twenty-two patients enrolled for off-pump coronary surgery received both a pulmonary artery catheter and a non-invasive cardiac output system for measurement of cardiac output. Data were compared by the Bland–Altman method to calculate the degree of agreement and to analyse if a significant difference existed between the two methods of cardiac output measurements. Results: Perioperatively, the non-invasive cardiac output underestimated cardiac output, but postoperatively overestimated it. The limits of agreement were larger during surgery compared to the postoperative period (−3.1; +2.5 vs. −1.4; +2.2 L min−1). Perioperatively, cardiac output measured with the pulmonary artery catheter varied from 0.5 to 7.5 L min−1 (mean 3.6 L min−1) and with the non-invasive cardiac output from 0.5 to 8.4 L min−1 (mean 3.9 L min−1). Postoperatively, these were 2.5–7.7 L min−1 (mean 4.5 L min−1) and 2.3–8.4 L min−1 (mean 4.9 L min−1), respectively. Conclusion: During off-pump cardiac surgery, the non-invasive cardiac output reliably measures cardiac output and does it more rapidly than a pulmonary artery catheter and may be more useful in order to detect rapid haemodynamic changes.