Impedance cardiography (ICG) has been proposed to estimate the stroke volume (SV) and cardiac output (CO) in various medical indications. The aim of this study was to explore the reliability of ICG during pregnancy with respect to SV and CO measurements. Blood pressure, heart rate and thoracic impedance were monitored during the course of pregnancy and related ICG patterns analyzed. We determined thoracic impedance (Z(0)), left ventricular ejection time (LVET) and the maximum value of the first derivative of the impedance waveform (dZ/dt)(max) beat-to-beat. The two main components of non-invasive SV estimation, LVET and (dZ/dt)(max), decreased in week 35 relative to week 12 by 7.6% ± 4.8% and by 36.0% ± 14.0%, respectively, based on a decrease in R-R interval of 9.9% ± 9.7%, whereas changes in Z(0) did not play a significant role. Furthermore, the decrease of (dZ/dt)(max) was greater in the third compared to the second trimester of pregnancy. Taking into account an 18.2% ± 6.8% body weight increase, the calculated SV decreased in week 35 relative to week 12 by 19.2% ± 14.3%. The normalized term ((dZ/dt)(max))/Z(0) explained 85-94% of the variance of SV change after week 20. These results were confirmed for fixed R-R interval at a constant value across the repeated measurements. Based on beat-to-beat analysis of the main components of non-invasive SV estimation by ICG, measured repeatedly throughout normal pregnancy, we conclude that SV calculations render invalid data. Our findings strongly suggest that CO cannot be reliably assessed with ICG in pregnant women.