Introduction: Pancreatic cancer and cholangiocarcinoma have historically been associated with particularly poor survival rates. The aim of this study was to identify temporal trends for these two malignancies in a national population cohort admitted to U.S. hospitals from the years 2005-2019. Methods: The National Inpatient Sample (NIS) database for the years 2005-2019 was queried to identify adult (age >18 years) patients admitted with the principal procedural codes for pancreatic cancer and cholangiocarcinoma. Data was obtained from US states. We estimated trends in the total number of patients yearly, prevalence, mortality, and mortality rate for patients admitted for pancreatic cancer and cholangiocarcinoma. Weighted analysis utilizing Stata 17 MP was performed. Results: A total of 1,406,778 patients had pancreatic cancer, of which 119,176 died. A total of 204,347 patients were found to have cholangiocarcinoma, of which 15,863 died. Throughout the years, there was an increase in the prevalence in pancreatic cancer from 0.19% to 0.33%, mortality rates decreased from 12% to 7.1% (p< 0.01), hospital length of stay decreased from 7.7 to 6.1 days (p< 0.01), total hospital charges increased from $37575 in 2005 to $73564 in 2019, Mean age remained the same 67.8 years in 2005 and 67 years in 2009 (p >0.05) (Table 1,2). Over the same timeframe, there was an increase in the prevalence of cholangiocarcinoma from 0.02% to 0.07%, mortality rates decreased from 11.4% to 7.4% (p< 0.01), hospital length of stay decreased from 8.8 days in 2005 to 6.6 days in 2019 (p< 0.01), total hospital charges increased from $35951 in 2005 to $83729 in 2019 (p< 0.01), mean age remained the same 67.9 years in 2005 and 68.3 years in 2019 (p< 0.01). Conclusion: Pancreatic cancer and cholangiocarcinoma continue to be among the deadliest malignancies in terms of mortality rate. However, over the past 15 years advancements have been made in ERCP and EUS which have allowed for an increased rate of diagnosis. Furthermore, mortality rates have significantly decreased in both diseases, which further highlights the importance and efficacy of these diagnostic interventions in treating these malignancies. This is the first NIS study to analyze trends in these two disease entities over this specific period (2005-2019). Our study also reflects that the advancements in our diagnostic modalities have likely significantly improved mortality rates and demonstrates the importance of further development of these modalities in the future. Table 1. - Prevalence and mortality rates of Pancreatic Cancer from 2005-2019 Year Total Prevalence Mortality (n) Mortality rate (%) P value (Moratlity rate) 2005 73,323 0.19% 8,929 12% p<0.05 2006 74,048 0.19% 8,179 11% p<0.05 2007 82,385 0.21% 8,041 9.8% p<0.05 2008 89,468 0.22% 8,757 9.8% p<0.05 2009 86,829 0.22% 8,162 9.4% p<0.05 2010 95,014 0.24% 7,894 8.3% p<0.05 2011 96,743 0.25% 7,785 8.0% p<0.05 2012 90,504 0.25% 7,105 7.8% p<0.05 2013 91.095 0.26% 7,015 7.7% p<0.05 2014 95,130 0.27% 7,360 7.7% p<0.05 2015 97,924 0.27% 3,757 7.7% p<0.05 2016 102,250 0.29% 7,615 7.4% p<0.05 2017 105,775 0.30% 8,320 7.8% p<0.05 2018 110,220 0.31% 8,220 7.4% p<0.05 2019 116,070 0.33% 8,280 7.1% p<0.05 Table 2. - Prevalence and Mortality Rate of Cholangiocarcinoma from 2005-2019. Year Total Prevalence (%) Mortality (n) (Mortality rate) P value (Mortality rate) 2005 7,205 0.02% 825 11.4% p < 0.05 2006 7,405 0.02% 687 9.2% p < 0.05 2007 8,849 0.02% 875 9.9% p < 0.05 2008 9,737 0.02% 908 9.3% p < 0.05 2009 10,069 0.03% 919 9.1% p < 0.05 2010 11,864 0.03% 931 7.9% p < 0.05 2011 11,468 0.03% 878 7.7% p < 0.05 2012 11,945 0.03% 800 6.7% p < 0.05 2013 12,750 0.04% 970 7.6% p < 0.05 2014 13,970 0.04% 1,075 7.6% p < 0.05 2015 11,060 0.04% 620 8.1% p < 0.05 2016 18,990 0.05% 1,410 7.4% p < 0.05 2017 20,745 0.06% 1,470 7.1% p < 0.05 2018 22,815 0.06% 1,600 7.0% p < 0.05 2019 25,475 0.07% 1,895 7.4% p < 0.05