Background. The aim of our study was to describe the efficacy of RBCx procedure using a Spectra Optia® automated apheresis system in children with sickle cell disease (SCD). Methods.We used automated red blood cell exchange to treat acute and chronic complications in 75 children with SCD who had a median age of 10 years [7-13]. We analysed 649 exchange sessions. Results. Peripheral venous access was limited in a number of the children, thus requiring a femoral central double‐lumen venous catheter. We recommend the use of heparin locking, with 500 units in each lumen of adouble‐lumen central venous catheter. This method was well tolerated, with few complications during the procedure. For preoperative prevention, all of the patients had achieved a post-RCE HbS level of <30%. For chronic transfusion, with a post-RCE Hb level of approximately 10-11 g/dL, a blood exchange volume of ≥32 mL/kg, and an interval between each RBCx procedure of ≤30 days, it is able to maintain the residual HbS level below 30%. For acute transfusion, a multiple logistic regression analysis showed that a post-exchange Hb level >=10 g/dL (p<0.001) and a total exchange volume >=35 ml/Kg (p = 0.001) are the best way to reduce the rate of HbS<30%. In this multivariate model, the area of the ROC curve was 0.84. Conclusion: Erythrocytapheresis is useful and safe for children with SCD. We recommend the use of heparin locking, with 500 units in each lumen of a double‐lumen central venous catheter.