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The mid-Piacenzian (~3 Ma) represents the most recent warm period in Earth's history on a geological time scale; it is characterized by a significant rise of global sea level. The simulation of the size and location of the ice sheets and the investigation of the uncertainty in the simulations are potentially helpful for constraining reconstructed sea level changes. In this study, we focus on the behavior of the Antarctic ice sheet (AIS) in the mid-Piacenzian. We investigate the influence of topography correction, model parameters, climate forcings, and model resolution on the modeled AIS and explore the isolated role of atmospheric and oceanic forcings. Forced by the simulated climate changes with the Norwegian Earth System Model, the Parallel Ice Sheet Model (15 km × 15 km) produces a nearly collapsed West AIS (WAIS) in the mid-Piacenzian, with no significant retreat of the East AIS (EAIS). The role of increased air temperature plays a key role in the mass loss of the mid-Piacenzian AIS, while its role is comparable to the role of ocean warming on the melting of the WAIS. In terms of the range of sea level changes, the largest source of uncertainty in the modeled AIS is derived from ice sheet model parameters and climate forcings. Although the employed model parameters, topography correction factors, and model resolution affect the simulated AIS in the mid-Piacenzian, large-scale deglaciation of the EAIS in our sensitivity experiments may only be possible with additional warming.