3D printing as an additive manufacturing method has proven to be of great interest for the computerized production of oral splints. Various parameters must be taken into consideration when assessing the durability of oral splints in a wet environment, such as the mouth. The aim of this in vitro study was to assess the wear behavior and water sorption of two 3D-printed splint materials depending on their building orientation and post-processing parameters. The parameters considered included the type of post-polymerization and the type of cleaning utilized after printing. The average wear depth was between −421.8 μm and −667.5 μm. A significant influence of the building orientation (p < 0.001) but not of the material (p = 0.810), cleaning (p = 0.933), or post-polymerization (p = 0.237) on wear was demonstrated. The water sorption ranged between 13.8 μg/mm3 and 30.3 μg/mm3, featuring a significant dependency on material and building orientation but not on cleaning (p = 0.826) or post-polymerization (p = 0.343). Material and fabrication methods should be carefully selected, because the type of material and building orientation affect the wear and water sorption of additively manufactured splint materials.