Impaired skeletal muscle quality is a major risk factor for adverse outcomes in acute respiratory failure. However, conventional methods for skeletal muscle assessment are inapplicable in the critical care setting. This study aimed to determine the prognostic value of computed tomography (CT) fatty muscle fraction (FMF) as a biomarker of muscle quality in patients undergoing extracorporeal membrane oxygenation (ECMO). To calculate FMF, paraspinal skeletal muscle area was obtained from clinical CT and separated into areas of fatty and lean muscle based on densitometric thresholds. The cohort was binarized according to median FMF. Patients with high FMF displayed significantly increased 1-year mortality (72.7% versus 55.8%, P = 0.036) on Kaplan-Meier analysis. A multivariable logistic regression model was built to test the impact of FMF on outcome. FMF was identified as a significant predictor of 1-year mortality (hazard ratio per percent FMF, 1.017 [95% confidence interval, 1.002-1.033]; P = 0.031), independent of anthropometric characteristics, Charlson Comorbidity Index, Simplified Acute Physiology Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction Score, and duration of ECMO support. To conclude, FMF predicted 1-year mortality independently of established clinical prognosticators in ECMO patients and may have the potential to become a new muscle quality imaging biomarker, which is available from clinical CT.