Differences in predictions of Glacial Isostatic Adjustment (GIA) for Antarctica persist due to uncertainties in deglacial history and Earth rheology. The Earth models adopted in many GIA studies are defined by parameters that vary in the radial direction only and represent a global average Earth structure (referred to as 1-D Earth models). Oversimplifying the actual Earth structure leads to bias in model predictions in regions where Earth parameters differ significantly from the global average, such as West Antarctica. We investigate the impact of lateral variations in lithospheric thickness on GIA in Antarctica by carrying out two experiments that use different rheological approaches to define 3-D Earth models that include spatial variations in lithospheric thickness. The first experiment defines an elastic lithosphere with spatial variations in thickness inferred from seismic studies.We compare the results from this 3-D model with results derived from a 1-D Earth model that has a uniform lithospheric thickness defined as the average of the 3-D lithospheric thickness. Irrespective of the deglacial history and sublithospheric mantle viscosity, we find higher gradients of present-day uplift rates (i.e. higher amplitude and shorter wavelength) in West Antarctica when using the 3-D models, due to the thinner-than-1-D-average lithosphere prevalent in this region. The second experiment uses seismically inferred temperature as an input to a power-law rheology, thereby allowing the lithosphere to have a viscosity structure. Modelling the lithosphere with a powerlaw rheology results in a behaviour that is equivalent to a thinner lithospheremodel, and it leads to higher amplitude and shorter wavelength deformation compared with the first experiment. We conclude that neglecting spatial variations in lithospheric thickness in GIA models will result in predictions of peak uplift and subsidence that are biased low in West Antarctica. This has important implications for ice-sheet modelling studies as the steeper gradients of uplift predicted from the more realistic 3-D model may promote stability in marine-grounded regions of West Antarctica. Including lateral variations in lithospheric thickness, at least to the level of considering West and East Antarctica separately, is important for capturing shortwavelength deformation and it has the potential to provide a better fit to Global Positioning System observations as well as an improved GIA correction for the Gravity Recovery and Climate Experiment data.