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Background and objectives: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) cannulas have major repercussions on vascular hemodynamics that can potentially lead to limb ischemia. Duplex ultrasound enables the non-invasive analysis of vascular hemodynamics. This study aims to describe the duplex parameters of the femoral vessels during V-A ECMO support, investigate differences between cannulated and non-cannulated vessels, and analyze the variations in the case of limb ischemia and intra-aortic balloon pumps (IABPs). Methods: Nineteen adults (≥18 years), supported with femoro-femoral V-A ECMO, underwent a duplex analysis of the superficial femoral arteries (SFAs) and veins (FVs). Measured parameters included flow velocities, waveforms, and vessel diameters. Results: 89% of patients had a distal perfusion cannula during duplex analysis and 21% of patients developed limb ischemia. The mean peak systolic flow velocity (PSV) and end-diastolic flow velocity (EDV) of the SFAs on the cannulated side were, respectively, 42.4 and 21.4 cm/s. The SFAs on the non-cannulated side showed a mean PSV and EDV of 87.4 and 19.6 cm/s. All SFAs on the cannulated side had monophasic waveforms, whereas 63% of the SFAs on the non-cannulated side had a multiphasic waveform. Continuous/decreased waveforms were seen in 79% of the FVs on the cannulated side and 61% of the waveforms of the contralateral veins were respirophasic. The mean diameter of the FVs on the cannulated side, in patients who developed limb ischemia, was larger compared to the FVs on the non-cannulated side with a ratio of 1.41 ± 0.12. The group without limb ischemia had a smaller ratio of 1.03 ± 0.25. Conclusions: Femoral cannulas influence flow velocities in the cannulated vessels during V-A ECMO and major waveforms alternations can be seen in all SFAs on the cannulated side and most FVs on the cannulated side. Our data suggest possible venous stasis in the FV on the cannulated side, especially in patients suffering from limb ischemia.