Hemodialysis patients who had received intradialytic parenteral nutrition (IDPN) during 1991 were identified. These patients were compared with unexposed controls after adjusting for demographic variables, baseline renal diagnosis, diabetic status, serum albumin (ALB), creatinine (CRE), and urea reduction ratio. At lower levels of ALB (≤3.4 g/dL), treatment with IDPN was associated with a reduction in the odds of death at 1 year, an effect that became stronger at lower levels of CRE (≤8.0 mg/dL). In contrast, treatment with IDPN in patients with normal ALB was associated with increased mortality. Time trend analyses of ALB and CRE demonstrated progressive increases toward pretreatment levels in IDPN recipients that were not evident in control subjects. These time trend data suggest that in undernourished hemodialysis patients, IDPN can effect the serum levels of valid biochemical surrogates of visceral and somatic protein nutrition. Albeit retrospective, the improvement in survival at year's end among patients with ALB ≤3.4 g/dL suggests that malnutrition and its attendant ill effects in hemodialysis patients may respond to aggressive therapeutic intervention, such as IDPN. These important findings should be prospectively confirmed in a randomized clinical trial.