Al-Li alloys are characterized by a strong anisotropy in mechanical properties and microstructure with respect to the rolling direction. Plates of 2198 Al-Li alloy were friction stir welded by employing maximum rotation speed: 1000 rev/min and welding speed of 80 mm/min, both in parallel and orthogonal directions with respect to the rolling one. The joints mechanical properties were evaluated by means of tensile tests at room temperature. In addition, fatigue tests performed with a resonant electro-mechanical testing machine under constant amplitude control up to 250 Hz loading, were conducted in axial control mode with R(σmin/σmax)=0.33, for all the welding and rotating speed conditions. The fatigue crack propagation experiments were performed by employing single edge notched specimens.With the aim to characterize the weld performances, both the microstructure evolution at jointed cross sections, related to the welding variables, and the fractured surfaces were respectively analyzed by means of optical and scanning electron microscopy.