Survival has been defined as an index of adequacy of dialysis. These hard data are the basis for comparing results obtained by different schedules or policies. The aim of the study was to assess mortality rate recorded within a system of tailored dialysis (1–6 dialysis per week in out-of-hospital settings: home hemodialysis, self- and limited care dialysis). Data recorded in a single center (1998–2003) were compared with data gathered in the Registry of Dialysis and Transplantation in the whole Region (1998–2000). Methods: Out-of-hospital dialysis unit is active since 1971, in which a new program integrating self- and limited care and home dialysis started since 1998. Patients: Incident dialysis patients starting renal replacement therapy within the program and all further patients starting dialysis in the Region in the same period were compared in an historical prospective cohort study. Results: 55 patients in the Unit and further 1443 patients in the whole Region started RRT since 1998. Main features of 55 patients were 32 males 23 females; median age 51 years, range 20–76; 72.7% displaying at least 1 comorbid factor. Throughout the period gross mortality rate was 4/125 patient-years in the Center. Kaplan–Meier curves showed a 1-year survival of 100% vs. 91%, respectively, in the Center and in the whole Region, and a 2-year survival of 95.5% vs. 76.6%, respectively, in the Center and in the whole Region (p = 0.001). The main demographic features were remarkably different in both settings (for the whole Region median age 66 years, range 2.2–101, at least 1 comorbidity in 56.9% of patients). In an attempt to correct for the different baseline characteristics, a multivariate Cox regression analysis was performed. The whole model resulted in statistically significant value (p = 0.000) and an increasing mortality risk resulted for age at starting dialysis, diabetes, and collagenopathy. In conclusion, tailored, high-efficiency dialysis policy may allow superior survival results. A longer follow up is needed to confirm our approach; in larger cohorts, the finding of a low mortality rate in a relatively young population with high comorbidity may underline the need to review our current concepts on dialysis adequacy.