The use of ketamine infusion for sedation/analgesia in patients receiving extracorporeal membrane oxygenation (ECMO) therapy has not been described. The aims of this retrospective cohort study were to explore whether ketamine infusion for patients requiring ECMO therapy was associated with altered RASS scores, decreased concurrent sedative or opioid use, or with changes in vasopressor requirements. All patients on ECMO who received ketamine infusions in addition to sedative and/or opioid infusions between December 2013 and October 2014 at Barnes-Jewish Hospital in St. Louis were retrospectively identified. Patient characteristics and process of care data were collected. A total of 26 ECMO patients receiving ketamine infusion were identified. The median (inter quartile range [range]) age was 40 years (30-52 [25-66]) with 62% male. The median starting infusion rate of ketamine was 50 mg/hr (30-50 [6-150]) and it was continued for a median duration of 9 days (4-14 [0.2-21]). Prior to ketamine, 14/26 patients were receiving vasopressor infusions to maintain hemodynamic stability. Ketamine initiation was associated with a decrease in vasopressor requirement in 11/26 patients within two hours, and 0/26 required an increase (p<0.001). All patients were receiving sedative and/or opioid infusions at the time of ketamine initiation; 9/26 had a decrease in these infusions within two hours of ketamine initiation, and 1/26 had an increase (p=0.02; odds ratio for decrease to increase = 9; 95% CI, 1.14 to 71.04). The median (IQR[range]) RASS score 24 hours before ketamine initiation was -4 (-3 to -5, [0 to -5]) and after ketamine was -4 (-3 to -4 [-1 to -5]) (P = 0.614). Ketamine infusion can be used as an adjunctive sedative agent in patients receiving ECMO and may decrease concurrent sedative and/or opioid infusions without altering RASS scores. The hemodynamic effects of ketamine may provide the benefit of decreasing vasopressor requirements.