Background/aim FloTrac/Vigileo is a noncalibrated arterial pressure waveform analysis for cardiac index (CI) monitoring. The aim of our study was to compare the CI measured by the 4th generation of FloTrac with PiCCO in septic shock patients. Materials and methods We simultaneously measured the CI using FloTrac (CIv) and compared it with the CI derived from transpulmonary thermodilution (CItd) as well as the pulse contour-derived CI using PiCCO (CIp). Results Thirty-one septic shock patients were included. The CIv correlated with CItd (r = 0.62, P < 0.0001). The Bland-Altman analysis showed a bias of 0.14, and the limits of agreement were –1.62–1.91 L/min/m2 with a percentage error of 47.4%. However, the concordance rate between CIv and CItd was 93.6%. The comparison of CIv with CIp (n = 352 paired measurements) revealed a bias of -0.16, and the limits of agreement were –1.45–1.79 L/min/m2 with a percentage error of 44.8%. The overall correlation coefficient between CIv and CIp was 0.63 (P < 0.0001), and the concordance rate was 85.4%. Conclusion The 4th generation of FloTrac has not acceptable agreement to assess CI; however, it has the ability to tracked changes of CI, when compared with the transpulmonary thermodilution method by PiCCO.