Purpose Ascertainment of mortality is critical to epidemiologic studies. Secondary collected database studies face challenges given the need to record mortality data in health claims or electronic medical records. The National Death Index (NDI) is the gold standard for mortality data in the U.S. Methods This study is a secondary analysis of an advanced cancer cohort in the U.S. between January 2010 and December 2018, with an established NDI linkage. Mortality data sources, inpatient discharge, disenrollment, death master file (DMF), Center for Medicare and Medicaid Services (CMS), Utilization management data (U.M.), and online obituary data were compared to NDI. We calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence intervals (95% CI). Per each source, death identified 60 days before and 30 days after NDI death was deemed a match. Results Among 40,692 patients, 25,761 (63.3%) had a death date using NDI; the composite algorithm had a sensitivity of 88.9% (95% CI= 88.5%, 89.3%), specificity was 89.1% (95% CI= 88.6%, 89.6%). At the same time, PPV was 93.4% (95% CI= 93.1%, 93.7%), NPV was 82.3% (95% CI= 81.7%, 82.9%), and when comparing each individual source, each had a high PPV but limited sensitivity. Conclusion The composite algorithm was demonstrated to be a sensitive and precise measure of mortality in advanced cancer patients in the U.S. from 2010 to 2018, while individual database sources were accurate but had limited sensitivity compared to the NDI.