Introduction: Acute kidney injury (AKI) is prevalent in critically ill patients, especially those needing extracorporeal membrane oxygenation (ECMO) due to cardiogenic shock or severe acute respiratory failure. The physiopathology of AKI in ECMO has not been clearly established, specific factors related to disease severity itself had to be associated with the development, but also factors from the ECMO system such as high flows, hemolysis, rhabdomyolysis, hemorrhage, and thrombosis have been described as possible causes of increased risk of AKI. Identifying and prioritizing these risk factors would contribute to reducing complications and outcomes associated with ECMO therapy Methods: A retrospective cohort study was conducted in 267 patients cannulated in venoarterial and venovenous ECMO support from 2020 to 2023 between January 1, 2020, and May 1, 2023. The development of AKI after ECMO initiation was identified, and an association of comorbidities, diagnosis previous to cannulation, severity scores, vasopressor need, anticoagulation, and transfusional therapy was compared in patients that developed AKI compared with those who did not. Results: 267 patients treated with ECMO were included in the study. A prevalence of 30% was documented for the appearance of AKI with longer ventilation days 19 vs 15 and higher mortality 57% vs 37% corroborated by higher severity scores. An elevated frequency of appearance of AKI is evidenced in patients with venovenous support compared to venoarterial support (54.8% vs 41.7% respectively). In relation to the severity of the disease, there was a greater requirement for vasoactive support with norepinephrine 77% and vasopressin 57%, in parallel, with transfusions 52%, as a surrogate of severity. Conclusions: Acute kidney injury is a significant concern in critically ill patients undergoing ECMO, with a wide-ranging incidence. The precise pathophysiological mechanisms remain elusive; however, several factors were identified such as vasopressor need, plasma and platelet transfusional therapy. Identifying these risk factors is crucial for optimizing ECMO management and reducing complications, thereby enhancing patient outcomes. Further research is needed to elucidate the exact mechanisms underlying AKI during ECMO and to devise targeted interventions for improved patient care.