There are conflicting clinical data on whether the use of a distal perfusion catheter (DPC) is beneficial for reducing the risk of limb ischemia in peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) patients. We investigated the hemodynamic effects of arterial cannula size, use of and size of a DPC, and ECMO flow (pump speed) on femoral artery hemodynamics in an adult peripheral VA-ECMO dynamic mock loop. The mock loop was tuned to heart failure conditions (cardiac output 3 L/min, arterial pressure 50 mm Hg, venous pressure 20 mm Hg). Three arterial cannulae (15Fr, 17Fr, 19Fr; right iliac) were each integrated into the loop with/without DPC (none, 5Fr, 8Fr; right superficial femoral artery [RSFA]), creating nine configurations tested. Hemodynamic pressures and flows were recorded over a range of pump speeds generating 0–3.5 L/min ECMO flow. The right femoral arteries demonstrated reduced flow, pressure, and pulsatility compared with the left across all cannula configurations and which worsened with increasing arterial cannula size and ECMO flow. Impaired right femoral hemodynamics were not improved with the use or size of DPC, suggesting that the increased resistance created by the presence of the arterial cannula and the DPC may be too great to overcome, thereby offsetting any potential flow benefits provided by the DPC.