A cohort retrospective study was used to analyze the effect of comorbidity on survival of end-stage renal disease (ESRD) patients undergoing dialysis. The authors analyzed the survival of 255 patients (144 men, 111 women; median age 54 years; range 8-81 years) followed at the District Hemodialysis Unit in Foggia, Italy, over a 15 year period (median follow-up 30 months; range 1-190 months). Two subscales assessing the overall severity of the identified coexistent diseases and overall physical impairment, and a composite four level index of coexistent diseases (ICED) were assembled using information recorded at the time of admission. The Cox proportional hazard model was applied to evaluate the association of various patient characteristics with the probability of death. Mortality risk was associated with patient age (RR = 3.4 for patients aged 42-61; RR = 4.8 for patients older than age 61 compared with patients younger than age 42), initial condition leading to renal failure (RR = 3.1 for diabetes compared with primary renal disease) and ICED (RR = 3.0 for patients with uncontrolled coexistent disease or severe impairment compared with patients with no coexistent disease and no or mild impairment). Gender and type of dialysis were not associated with mortality risk. It was concluded that, as is the case with other chronic conditions, co-morbidity is a powerful independent prognostic factor in determining the mortality of ESRD patients.