The aim of this study was to explore the association between arterial return cannula diameter and hemolysis during peripheral VA ECMO. We identified 158 adult patients who received peripheral VA ECMO at our institution from the national ECMO database (EXCEL) between January 2019 and July 2021. We classified patients into a small cannula group (15 Fr diameter, n = 45) and a large cannula group (≥17 Fr diameter, n = 113), comparing incidences of clinical hemolysis and plasma free hemoglobin (pfHb). Moderate hemolysis is defined as having pfHb 0.05–0.10 g/L and severe hemolysis as having pfHb >0.10 g/L sustained for at least two consecutive readings or leading to a circuit change. There were no significant differences in rates of moderate hemolysis between small and large cannula groups (1 vs. 6; p = 0.39) and severe hemolysis (0 vs. 3; p = 0.27), nor was the pfHb level significantly different at 4 hours (0.086 ± 0.096 vs. 0.112 ± 0.145 g/L; p = 0.58) and at 24 hours (0.042 ± 0.033 vs. 0.051 ± 0.069 g/L; p = 0.99). There were no increased rates of hemolysis when comparing small versus large arterial return cannula diameter in peripheral VA ECMO.