We conducted a study of the influence of the vasoactive peptides atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) on survival of patients on hemodialysis and their association and relative importance with cardiac and clinical variables. Thirty-three hemodialysis patients were characterized by age, sex, diagnosis, blood pressure, serum (S)-albumin, serum (S)-urea, hemoglobin, dialysis dose, weight gain, duration of dialysis, cardiac hypertrophy, volume, failure, and ischemia and plasma levels of ANP and NPY. The outcomes were analyzed for early deaths (<1 year) and for all deaths. The association of the variables to early deaths and all deaths, respectively, was studied in Cox proportional hazard analyses. The variables were also studied in three hierarchical steps: clinical variables only, clinical and cardiac variables, and all variables. For all deaths, the independent variables were plasma NPY (pmol/L) (hazard ratio [HR] = 1.035, p = 0.004), heart volume (ml/m2) (HR = 1.009, p = 0.001), and S-albumin (g/L) (HR = 0.750, p = 0.034). For early deaths, the independent variables were predialysis ANP (pmol/L) (HR = 1.008, p = 0.034) and NPY (pmol/L) (HR = 1.031, p = 0.026). In the hierarchical study, excluding the vasoactive peptides, heart volume, heart failure and S-albumin were independently associated with all deaths, and mean arterial blood pressure was associated with early death. When also excluding the cardiac parameters, S-albumin was associated with all deaths and mean arterial blood pressure with early death. In conclusion, plasma levels of the vasoactive peptides ANP and NPY are the most important group in a hierarchy of variables that predict imminent death in hemodialysis patients, and NPY is associated with late death. ANP and NPY apparently sum up the detrimental influence of many factors in hemodialysis patients.