Fluid overload in acute respiratory distress syndrome is associated with increased mortality. The purpose of this study was to investigate the association of cumulative fluid balance (CFB) during the first 7 days of eno-venous extracorporeal membrane oxygenation (VV ECMO) and mortality. Adult patients on VV ECMO for greater than 168 hours, between November 2015 and October 2019, were included. CFB during the first 7 ECMO days was compared between survivors and nonsurvivors, and survival was analyzed using Kaplan-Meier analysis and cox proportional hazards modeling. One hundred forty-six patients were included. Median age was 45 years [32, 55], respiratory ECMO survival prediction score was 3 [0, 5], and P/F ratio was 70 [55, 85]. CFB for ECMO days 1–3 was +2,350 cc [–540, 5,941], days 4–7 –3,070 cc [–6,545, 437], and days 1–7 –341 cc [–4,579, 5,290]. One hundred seventeen patients (80%) survived to hospital discharge. Survivors were younger (41 years [31, 53] vs. 53 years [45, 60], p < 0.001) and had a higher respiratory ECMO survival prediction score, (3 [1, 5] vs. 1.5 [–1, 3], p = 0.002). VV ECMO survivors had a significantly more negative CFB during the first 7 days of VV ECMO (–1,311 cc [–4,755, 4,217] vs. 3,617 cc [–2,764, 9,413], p = 0.02), and CFB was an independent predictor of 90 day mortality (HR = 1.07 [1.01, 1.14], p = 0.02). Further studies are needed to determine the causal relationship between fluid balance and survival during VV ECMO.