Therapeutic plasma exchange (TPE) is used for a variety of illnesses in critically ill pediatric patients. Although both centrifugation and filtration are known to be effective methods, to our knowledge, clinical results for TPE by these methods are not compared in pediatric patient populations. One hundred patients who had TPE for a variety of diagnoses were included in the study. In 55 patients plasma exchange was implemented by centrifugation and in 45, by filtration. These two groups were further divided into subgroups according to admittance diagnoses. The demographic information, admittance Pediatric Risk of Mortality scores, Pediatric Logistic Organ Dysfunction (PELOD) scores before beginning of therapy and PELOD at the end of therapy, durations of ventilatory support, pediatric intensive care unit and hospital stay, and outcomes were compared. Although the survival was significantly better in filtration group, it included more patients with neurologic diagnoses. Filtration group standard mortality rate was 0.6. In both groups, the PELOD scores after the termination of TPE were significantly decreased compared to that before beginning of TPE. Within thrombotic microangiopathy and hemophagocytic lymphohistiocytosis subgroups, median PELOD scores before treatment were higher in centrifugation patients but survival was similar with both methods. Both methods of TPE are alike in decreasing PELOD scores. In the filtration group, survival benefit of TPE is evident. In thrombotic microangiopathy patients, despite higher PELOD scores in the centrifugation group, survival is similar for both methods. These findings should be retested in randomized studies and the underlying physiology awaits to be uncovered.