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OBJECTIVE To investigate whether prior statin therapy is associated with an improvement in mortality among patients who undergo extracorporeal membrane oxygenation (ECMO) therapy. DESIGN Retrospective, population-based, cohort study. SETTING Health records were obtained from the National Health Insurance Service database in South Korea. PATIENTS All adult patients (≥18 y) who underwent ECMO therapy in the intensive care unit between 2005 and 2018 were enrolled. EXPOSURES Statin users were defined as patients who were prescribed continuous oral statins ≥90 days before ECMO. MEASUREMENTS AND MAIN RESULTS The primary endpoint of this study was 90-day mortality. A total of 21,129 adult patients from 128 hospitals were included (4,737 [22.4%] statin users and 16,392 [77.6%] nonusers). After propensity score matching, 9,474 ECMO patients (4,737 in each group) were included in the final analysis. In the propensity-score-matched cohort, statin users exhibited lower 90-day mortality than did nonusers (58.6% [2,774/4,737] in statin users v 65.6% [3,106/4,737] in nonusers). In addition, on Cox regression, 90-day mortality in statin users was 14% less than that in nonusers (hazard ratio 0.86, 95% confidence interval 0.81-0.90; p < 0.001). CONCLUSION Among patients who underwent ECMO in South Korea, prior statin therapy was found to be associated with lower 90-day mortality rates after ECMO therapy. However, because this study had a retrospective design, future prospective trials are needed to confirm the findings.