Few data are available on the accuracy of death classification in patients with end-stage renal disease (ESRD). The National Institutes of Health-funded Hemodialysis (HEMO) Study allows the opportunity to compare cause of death recorded on the Health Care Financing Administration (HCFA) Death Notification Form 2746 with death classified by the HEMO Study. The HEMO Study cause of death is determined by trained HEMO Study Outcome Review Committee physicians. In this interim analysis, there were 220 deaths coded by both classification systems. Using the HEMO Study classification system, the most common cause of death was ischemic heart disease (20.4%), followed by arrhythmia and conduction problems (10.4%), cerebrovascular disease (8.6%), and non-access-related infections (7.7%). Using the HEMO Study final death classification as the reference standard, most differences in the two classification systems were related to coding of heart disease. Sensitivity for the HCFA classification ranged from 9.1% for congestive heart failure to 91.7% for malignancy, whereas specificity values were all greater than 78%. Positive predictive values ranged from 11.8% for other heart disease and conditions to 100% for malignancy and hepatobiliary disease, whereas negative predictive values were all greater than 85%. The kappa statistic between the two death classification systems ranged from 0.12 for congestive heart failure to 0.95 for malignancy. Studies using death classification from the HCFA ESRD death notification form for deaths secondary to either cardiovascular diseases or unknown causes should be interpreted cautiously.