A large percentage of patients on extracorporeal membrane oxygenation (ECMO) require continuous renal replacement therapy (CRRT) usually performed through a different venous access or by introducing a filter into the ECMO circuit. Here, we evaluated the efficacy and safety of including a CRRT machine in the circuit by connecting its inlet line after the centrifugal pump and its outlet line before the oxygenator. We tested the function of the combined system initially in a closed circuit, followed by an experimental animal study, and, finally, in a clinical trial with six children. Both machines functioned adequately and there were no significant changes in the pressures of the ECMO circuit after the introduction of the CRRT device, thus achieving the preset negative balances and normalization of the serum urea and creatinine concentrations. The mean life of the filters was about 138 h, and only one filter needed changing due to clotting. Our study shows that the introduction of a CRRT device into the ECMO circuit is a safe and effective technique that improves fluid balance, increases filter life, and does not cause complications. For these reasons, this may be a good method for performing CRRT in patients on ECMO.