Chronic inflammation may play an important role in early morbidity and mortality in hemodialysis (HD) patients. Interleukin-6 (IL-6) production is enhanced in long-term HD patients and this activated phase response has been shown to be a predictor of cardiovascular disease in the uremic syndrome as well as in the general population. Furthermore, IL-6 and C-reactive protein (CRP) have been negatively related to low serum albumin levels (MIA syndrome). Several studies have attempted to address the question as to whether the type of the dialysis membrane, the quality of the dialysate, and the dialysis technique may be responsible for the induction of a chronic inflammatory state. Recently, the Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown that high-efficiency hemodiafiltration (HDF)- treated patients had a better survival than HD-treated patients accounting for sex, dialysis dose, co-morbid condition and country specificities. Here we report data from the RISCAVID study, an observational and prospective trial including the whole chronic HD population in the north-west part of Tuscany (1,235 million people). The aim of the study was to elucidate the relevance of traditional and non-traditional risk factors on mortality and morbidity in HD patients as well as the impact of different HD modalities. Data at 30 months from this study showed the synergic effect of CRP and pro-inflammatory cytokines as the strong predictors of overall and cardiovascular mortality. HDF was associated to an improved cumulative survival independently of dialysis dose.