BackgroundPancreatic cancer (PC) is one of the most lethal cancers around the world. A high body mass index (BMI) is recognized as a significant and modifiable risk factor for this disease.MethodsData were obtained from the Global Burden of Disease (GBD) 2021 study. We used joinpoint regression and age-period-cohort (APC) models for trend analysis, and the Autoregressive Integrated Moving Average (ARIMA) model to forecast the burden of high BMI-related PC in 2022-2041. In addition, we used decomposition and health inequality analyses to examine causes and regional inequalities in the burden of high BMI-related PC.ResultsFrom 1990 to 2021, the total number of deaths from high BMI-related PC increased nearly tenfold. In the last 30 years, females consistently bore a greater burden of BMI-related PC, whereas the increase among males was more substantial. Deaths from high BMI-related PC escalated by 7 to 12 times in the 20-49 age group and by over sevenfold in low social development index (SDI) regions, reflecting increasing risk in younger populations and worsening global health inequalities. Furthermore, we predict that the global age-standardized mortality rate (ASMR) will continue to increase over the next 20 years.ConclusionOur findings generally revealed a sharply increased trend for the global burden of PC associated with high BMI during the past 30 years, as well as pronounced disparities by sex, age, and region. Hence, countries and nations should urgently advocate targeted public health initiatives in the future, especially in high-burden regions and populations.