Background: Vascular complications remain a prevalent and devastating complication of extracorporeal membrane oxygenation (ECMO). Risks for vascular complications have risen as the volume and medical complexity of ECMO cases has rapidly increased in recent years. This study assesses occurrence and clinical impact of vascular complications across all ECMO modes and cannulation methods in a high-volume academic center. Methods: A retrospective single-institution review was performed of all ECMO cannulations for central or peripheral venovenous (VV) or venoarterial (VA) ECMO in 2019-2020. Patients who expired during cannulation were excluded. Primary outcomes of vascular consultation rates at or after ECMO placement, limb loss, and mortality were assessed during index hospitalization. Results: A total of 229 patients were identified during the 2-year study period. VA ECMO was used in the majority of patients (n = 137, 60%), with 83% (N = 114) undergoing peripheral cannulation. Vascular surgery was consulted in 54 (23.6%) patients. Complication rates ranged from 33.9% in peripheral VA cannulation to 7% in jugular VV cannulation. Overall, 65% of vascular consults required operative intervention; interventions were highest in peripheral VA ECMO (n = 30 of 114, 26.3%). Across all ECMO types, acute limb ischemia (ALI) was the most common complication (n = 38, 16.5%), with rates ranging from 26.1% in central VA ECMO to 4.8% in jugular VV ECMO. Distal antegrade perfusion catheters (DPCs) were employed in n = 68 of 114 (59.6%) of all peripheral VA ECMO cases. Prophylactic DPCs were found to be incorrectly placed in 10.2% (n = 7 of 68) of cases, which obscured the ability to fully evaluate the effect of prophylactic DPCs on reducing rates of ALI. Major amputation (Below Knee Amputation/Above Knee Amputation) occurred in six peripheral VA patients (5.3%), two central VA patients (8.65), and two femoral-femoral VV patients (4%). Patients with ALI experienced significantly lower rates of in-hospital survival in Kaplan-Meier analysis (32.5% vs 54%, log-rank = 0.023). Conclusions: This study highlights the prevalence of vascular complications, and their associated mortality impact, across all modes of ECMO and additionally identifies several areas for institutional performance improvement. ALI was the most common complication across all cohorts and was associated with decreased in-hospital survival. The impact of DPC on ALI was difficult to elucidate due to nonstandardized placement patterns and selective use. In the care of these medically complex patients on multidisciplinary teams, review of outcomes and group discussions targeting areas for improvement are critical to success; in this study, findings resulted in the development of a lower extremity perfusion management protocol.