Although many epidemiologists use the National Death Index (NDI) as the "gold standard" for ascertainment of US mortality, high search costs per year and per subject for large cohorts warrant consideration of less costly alternatives. In this study, for 1995-2001 deaths, the authors compared matches of a random sample of 11,968 National Institutes of Health (NIH)-AARP Diet and Health Study subjects to the Social Security Administration's Death Master File (DMF) and commercial list updates (CLU) with matches of those subjects to the NDI. They examined how varying the lower limits of estimated DMF match probabilities (m scores of 0.60, 0.20, and 0.05) altered the benefits and costs of mortality ascertainment. Observed DMF/CLU ascertainment of NDI-identified decedents increased from 89.8% to 95.1% as m decreased from 0.60 (stringent) to 0.20 (less stringent) and increased further to 96.4% as m decreased to 0.05 (least stringent). At these same cutpoints, the false-match probability increased from 0.4% of the sample to 0.6% and then 2.3%. Limiting NDI cause-of-death searches to subjects found in DMF searches using less stringent match criteria, further supplemented by CLU vital status updates, improves vital status assessment while increasing substantially the cost-effectiveness of ascertaining mortality in large prospective cohort studies.