To systematically evaluate the effect of small changes in transducer position on key hemodynamic variables including CO generated by 4th generation FloTrac software. After cardiac surgery, cardiac output, mean arterial pressure, systemic vascular resistance, and stroke volume variation were measured with 4 generation Flotrac software. The transducer position was randomly placed at the midaxillary plane, 4 cm higher than the midaxillary plane or 4 cm lower than the midaxillary plane. Averages of three measurements were used. Data was available from 20 patients. Cardiac output increased from 4.59 L/min (± 0.92) to 4.78 L/min (± 0.99) with the transducer position at the midaxillary plane to 4 cm higher than the midaxillary plane, and cardiac output decreased to 4.43 L/min (± 0.90) with the transducer 4 cm lower than midaxillary plane (P < 0.001). On the relative scale, CO increased 4.1% (95% CI 3.1-5.0) when comparing the higher transducer level with the midaxillary plane position, and CO decreased 3.4% (95% CI 2.4–4.4) when comparing the midaxillary plane position with the lower transducer level, correspondiong to changes in CO of ≈ 1% per 1 cm change in transducer position. Mean arterial pressure and systemic vascular resistance both changed significantly with transducer position (both P < 0.001), whereas no statistically or clinically significant effect was seen on stroke volume variation (P = 0.98). A four-centimeter change in vertical transducer position induced clinically significant changes in cardiac output measurements by 4th generation FloTrac software. Definitions of optimal cardiac output in goal-directed therapy algorithms require meticulous transducer adjustment and can only be used in the reference patient position.