Objective: The objectives of this study were to determine the feasibility and safety of simultaneous renal replacement therapy (RRT) during extracorporeal membrane oxygenation (ECMO) support for postcardiotomy patients with cardiogenic shock and whether simultaneous RRT with ECMO would improve survival and reduce morbidity. The authors hypothesized that simultaneous RRT could facilitate effective fluid management and rapid metabolic control in postcardiotomy patients with cardiogenic shock who were undergoing ECMO support. Design: A parallel, open-label, single-center pilot randomized trial. Setting: University-affiliated cardiac surgery intensive care unit. Participants: The study comprised 41 postcardiotomy patients with cardiogenic shock who received ECMO support. Interventions: Participants were enrolled and randomly assigned via a 1:1 allocation to a simultaneous RRT arm versus a standard care arm. The patients in the simultaneous RRT arm received RRT within 12 hours of the start of ECMO regardless of the conventional RRT indication. Simultaneous RRT was delivered with the RRT machine connected to the ECMO circuit. The patients in the standard care arm did not receive RRT at the start of ECMO unless the conventional RRT indications were fulfilled. Measurements and Main Results: All 41 patients enrolled were followed-up for 30 days and the results analyzed. The primary feasibility outcome was the time from randomization to simultaneous RRT of <12 hours in the simultaneous RRT arm. All participants in simultaneous RRT arm fulfilled with a median time from randomization to simultaneous RRT of 4.4 (2.7-5.6) hours. The 30-day all-cause mortality was 61.9% in the simultaneous RRT arm and 75.0% in the standard care arm (p = 0.51). The lactate clearance was higher in the simultaneous RRT arm (0.56 ± 0.4 v 0.28 ± 0.4 mmol/L/h; p = 0.04). There was lower cumulative fluid balance in the simultaneous RRT arm on ECMO day 3 (–1,510 [–3560 to 1,162] v –332 [–2,027 to 2,181]; p = 0.38) and ECMO day 5 (–2,671 [–5,197 to 3,334] v –1,509 [–3,595 to 1,162]; p = 0.41) without significance. There were no significant differences in adverse events reported and no hemodynamic instability owing to simultaneous RRT delivery. Conclusions: This pilot study suggests the feasibility and safety of simultaneous RRT during ECMO support for postcardiotomy patients with cardiogenic shock, providing an efficient means for controlling fluid status and metabolics. A large trial based on this pilot study is required to confirm the clinical benefits. © 2019 Elsevier Inc.