During the last years welded titanium components have been extensively applied in aeronautical and aerospace industries because of their high specific strength and corrosion resistance properties. Friction Stir Welding (FSW) is a solid state welding process, currently industrially utilized for difficult to be welded or “unweldable” aluminum and magnesium alloys, able to overcome the drawbacks of traditional fusion welding techniques. When titanium alloys are concerned, additional problems arise as the need for very high strength and high temperature resistant tools, gas shield protection and high stiffness machines. Additionally, the process is characterized by an elevated sensitivity to temperature variations, which, in turn, depends on the main operative parameters. Numerical simulation represents the optimal solution in order to perform an effective process optimization with affordable costs. In this paper, a fully 3D FEM model for the FSW process is proposed, that is thermo-mechanically coupled and with rigid-viscoplastic material behavior. Experimental clamping parts are modeled and the thermal loads are calculated at the varying of the cooling strategy. Finally, the effectiveness of the cooling systems is evaluated through experimental tests.