Hemodialysis (HD) is an intermittent procedure during which large fluid and electrolyte shifts occur. We hypothesized that sudden death occurrences in HD patients are related to the timing of HD, and that they occur more frequently in the 12 h period starting with dialysis and in the 12 h period at the end of the dialysis-free weekend interval. In a retrospective study, 228 patient deaths were screened to determine if they met the criteria for sudden death. Information was obtained from clinic charts, dialysis center records, and interview of witnesses of the death event. There were 80 HD patients who met the criteria for sudden death. A bimodal distribution of death occurrences was present, with a 1.7-fold increased death risk occurring in the 12 h period starting with the dialysis procedure and a threefold increased risk of death in the 12 h before HD at the end of the weekend interval (P=0.011). Patients with sudden death had a high prevalence of congestive heart failure and coronary artery disease. Only 40% of patients experiencing sudden death were receiving beta-blockers, and the prior monthly serum potassium value was less than 4 mEq/l in 25%. Sudden death is temporally related to the HD procedure. Every other day HD could be beneficial in preventing sudden death. Careful attention to the usage of beta-blockers and to the maintenance of normal serum potassium values is indicated in HD patients at risk for sudden death.