This study describes the largest North American single-institution experience with adult patients requiring multiple extracorporeal membrane oxygenation (ECMO) runs in the same admission and aims to describe outcomes of survival and complication rates in this patient population. A retrospective chart review-based study in a single quaternary care center of venoarterial (VA) ECMO patients cannulated multiple times on ECMO support to assess for outcomes and survival (both of ECMO therapy and survival to discharge). Single quaternary academic center for ECMO. All patients undergoing VA ECMO who were at least 18 years of age from 2011 to 2019, composed of a total of 14 patients requiring multiple cannulations. None, this was a retrospective chart review. Of the 326 patients reviewed, 14 patients (4.3% of all patients in the database) had multiple ECMO therapies. The average patient age was 55.2 ± 10.99 years of age, and 57% were female; 4 of the 14 (28.6%) patients survived to hospital discharge. The top 2 indications for initial VA ECMO therapy were cardiogenic shock after myocardial infarction (35.7%) and after cardiotomy shock (35.7%). For repeated cannulation, the most common cause was hypoxia (64%, 9 patients), with 6 of these patients requiring a right ventricular assist device plus oxygenator. Other causes for repeated cannulation included post-cardiotomy shock (14%), recurrent ventricular tachycardia (14%), and cardiogenic shock (7%). All patients who required continuous venovenous hemofiltration during their first run of ECMO did not survive to discharge. Fourteen of 326 patients in the authors' VA ECMO database required additional ECMO therapy after decannulation; this represents at least 1 to 2 cases per year at higher-volume centers. Despite the small number of patients in this retrospective review, it seems that certain patients are reasonable candidates for additional ECMO therapy should their cardiopulmonary function again decline. The findings of renal replacement therapy and infection being more common during a second ECMO run are logical, but larger cohorts (ideally multicenter or from within the Extracorporeal Life Support Organization registry) are required to validate these preliminary findings. Copyright © 2019 Elsevier Inc. All rights reserved.