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Oak-pine forests in the U.S. Central Hardwood Forests are recovering from exploitative harvesting and clearing in the early twentieth century and are undergoing rapid succession changes. Unprecedented red oak borer (ROB, Enaphalodes rufulus) outbreaks in 1999–2003 are associated with the largest oak mortality event reported in the Central Hardwood Region since the arrival of Europeans. Predicting and evaluating the effects of ROB disturbance on forest composition has practical value for forest management plans that aims to minimize ecological and economic loss from ROB disturbances. However, such prediction at a regional scale is rare due to the limited approaches that could explicitly couple insect outbreak mechanisms with forest dynamics under changing climate. We used a newly developed climate-sensitive Biotic Disturbance Agent module in the LANDIS PRO framework to simulate species composition changes due to succession, climate change, and ROB disturbances in 13.5 million ha forests in the U.S. Central Hardwood Region from 2000 to 2300. Our simulation suggested that succession is more important than climate effects and ROB disturbance in predicting regional species composition changes. ROB disturbance interacting with climate change accelerated the decline of primary host species (e.g., Quercus rubra) and then substantially changed forest succession trajectories under warming climates. Our modeling approach improved the simulation realism of ROB disturbance and more realistically projected how tree species will respond to ROB disturbance under changing climate, informing decision-making in silvicultural prescriptions and long-term management plans. [ABSTRACT FROM AUTHOR]