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Pancreatic cancer is a significant public health problem worldwide. It is currently ranked as the 12th most common malignancy and the 6th leading cause of cancer mortality. This study aimed to investigate sex-specific and age-specific pancreatic cancer mortality trends and disparities in the Serbia from 2000 to 2021. A descriptive epidemiological population-based study analyzing pancreatic cancer mortality was conducted. Age-standardized mortality rates (ASMRs) were calculated using the Segi's world standard population. Temporal trends for pancreatic cancer mortality were assessed using the joinpoint regression analysis. Age-standardized rate of pancreatic cancer in Serbia was 6.4/100,000 (7.9/100,000 in men, 5.1/100,000 in women). The rates were found to be 1.6 times higher in men than women. Pancreatic cancer mortality trend significantly increased from 2000 to 2010 in men (APC=+2.4%, 95%CI: 0.3 – 1.4), after 2010 rates nonsignificantly decline (APC=−0.4%; (95%CI: −2.5 – 0.5). In women, mortality trend significantly increased by +1.8% at an annual level (95%CI: 0.7–2.7). The mortality of pancreatic cancer increased by age. The joinpoint analysis showed a significant rising trend of mortality rates in all age groups 60+, with the highest average annual percent change being reported in the age groups 85+ (AAPC=+3.1 (95%CI: 1.6–4.5)). The provision of updated statistics on the occurrence and outcomes of pancreatic cancer, time trends among various population groups, along with a better understanding of its etiology and identification of causal changeable risk factors – are essential when it comes to the primary prevention of this particular disease.