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Purpose: To examine mortality trends among non-Hispanic (NH) adults with pancreatic cancer., Method: CDC-WONDER database was used to extract death certificate data on pancreatic cancer-related mortality in NH adults aged ≥ 45 from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent changes (APCs) were calculated and stratified by year, age, sex, race, and region., Results: From 1999 to 2020, 783,772 deaths occurred among middle-aged (45-64) and older (65-85 +) NH adults. Overall AAMR increased from 31.7 in 1999 to 33.8 in 2020 (APC: 0.35; 95% CI:0.28-0.41). NH older adults had higher AAMRs (67.9) than NH middle-aged adults (12.5). Men consistently had higher AAMRs (37.7) than women (28.4). NH African Americans had the highest AAMRs (40.8) compared to NH Whites (32.1), NH American Indians (23.9), and NH Asians (22.4). Metropolitan areas had a higher AAMR (32.7) than non-metropolitan areas (32.2). The Northeast region had the highest AAMR (34.0) followed by Midwest (33.2), South (32.2), and West (30.1). Delaware, District of Columbia, Louisiana, Michigan, and Mississippi had the highest AAMRs among states., Conclusions: Pancreatic cancer-related mortality among NH adults has increased from 1999 to 2020. Highest AAMRs were reported in older men, NH African Americans, the Northeastern and metropolitan areas., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)