Obesity is associated with an overall increased risk of morbidity and mortality. However, in patients with critical illness, sepsis, and acute respiratory distress syndrome, obesity may be protective, termed “the obesity paradox.” This is a systematic literature review of articles published from 2000 to 2022 evaluating complications and mortality in adults with respiratory failure on veno-venous extracorporeal membrane oxygenation (VV ECMO) based on body mass index (BMI). Eighteen studies with 517 patients were included. Common complications included acute renal failure (175/377, 46.4%), venous thrombosis (175/293, 59.7%), and bleeding (28/293, 9.6%). Of the six cohort studies, two showed improved mortality among obese patients, two showed a trend toward improved mortality, and two showed no difference. Comparing all patients in the studies with BMI of less than 30 to those with BMI of greater than or equal to 30, we noted decreased mortality with obesity (92, 37.1% of BMI <30 vs. 30, 11% of BMI ≥30, p ≤ 0.0001). Obesity may be protective against mortality in adult patients undergoing VV ECMO. Morbid and super morbid obesity should not be considered a contraindication to cannulation, with patients with BMI ≥ 80 surviving to discharge. Complications may be high, however, with higher rates of continuous renal replacement therapy and thrombosis among obese patients.