Venoarterial extracorporeal membrane oxygenation (VA ECMO) is an effective mechanical circulatory support for cardiopulmonary failure. Conventionally, an arterial cannula over 15 Fr is inserted for full circulatory support in peripheral VA ECMO. However, limited data are available regarding the impact of cannula size on clinical and procedural outcomes. Between January 2014 and April 2016, 165 patients underwent peripheral VA ECMO with femoral artery cannulation were enrolled in a single-center registry. We classified patients into two groups according to the arterial cannula’s size: “small cannula group” (14-15 Fr, n = 87) and “large cannula group” (16-21 Fr, n = 78). We compared the clinical outcomes and procedural-related complications between the two groups. Neither the survival to discharge (51.7% in the small cannula group vs. 57.7% in the large cannula group; p = 0.44) nor the weaning success rate (70.1% vs. 64.1%; p = 0.41) was significantly different between the two groups. There was no significant difference in initial ECMO flow/body surface area between the two groups (1.86 ± 0.42 vs. 1.98 ± 0.49 L/min/m; p = 0.12) although small cannula group had a numerically low value. The small cannula group showed significantly shorter ECMO duration time (2.6 [0.7-5.2] vs. 4.0 [1.3-7.8] day; p < 0.01). Also, lower limb ischemia was significantly lower in the small cannula group (4.6% vs. 15.4%; p = 0.02). In peripheral VA ECMO, as compared with the large cannula strategy, the small arterial cannula strategy showed similar clinical outcomes and a decrease in lower limb ischemia.