Among hemodiafiltration (HFD) techniques, hemodiafiltration reinfusion (HFR) seems unable to achieve an optimal depurative efficacy. This study aimed to evaluate whether the HFR technique as suggested in its original configuration could be improved by devising a new technique (post-dilution HFR (PDHFR)) inverting the purification sequence to increase the purification efficiency of the entire system.We performed standard HFR in six uremic patients during 6 months and, subsequently, during a further 6 months, PDHFR was performed. The dialytic efficacy of the two techniques and the filter blood rest were evaluated. In addition, we studied the behavior of cytokines during the inverted HFR sessions.We observed a significant increase in urea extraction and in Kt/V. An equally significant improvement was observed with regard to beta2-microglobulin (beta2-m) extraction and blood rest. Furthermore, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) significantly decreased after inverted HFR treatment.The inversion of the original configuration allowed us to improve the depurative efficacy of standard HFR, increasing the removal of both urea and beta2-m, and reducing the blood rest. Finally, it was notable that the reduction in cytokine levels could attenuate the uremic microinflammatory state.