In copper extrusion, billet temperatures of 600°C or more are very common and the dies are therefore exposed to high thermo-mechanical stress. This causes deflection and wear of the dies and thus reduced quality of the extruded profile. In the present study, die deflection and residual deformation after several extrusion cycles was investigated by means of extrusion trials and numerical analyses. Material models of four tool materials (hot-work tool steels 1.2367 and CS1, nickel-based alloy 718, cobalt-based alloy Stellite 1) and the copper alloy CW024A were provided by hot compression tests. Extrusion trials were carried out applying four different dies, each made of another tool material. Using the FEM based software DEFORM 2D, the extrusion trials were modeled and decoupled die stress analyses were performed, which simulated three consecutive load cycles. The focus of the data interpretation was in die deflection in proximity of the die land due to the thermo-mechanical load and residual plastic deformation after relief of the mechanical load. Larger values of deflection close to the die land were observed for the hot-work tool steels, while the deflection of nickel- and cobalt-based alloys was negligibly small. Also, remarkable plastic deformation was only determined for the hot-work tool steels, with increasing values for every simulated load cycle. This analysis characterizes the performance limits of hot-work tool steels and the benefits of nickel- and cobalt-based alloys regarding contour accuracy during high temperature copper extrusion.