Friction stir processing (FSP) is an advanced technology of surface modification of microstructure of metals and alloys in order to improve mechanical and operational properties. Previous works on processing of titanium alloys demonstrated that variation of FSP process variables (such anticlockwise rotation rate, processing speed and plunge force) significantly influences on evolution of microstructure and mechanical properties of Ti6Al4V alloy. However, the influence of multipass FSP on Ti6Al4V alloy has not been studied. Thus, this work studied the influence of four-pass FSP of Ti6Al4V titanium alloy on evolution of microstructure and mechanical properties of this alloy. Analysis of the microstructure has demonstrated that, in the stir zone, a heterogeneous microstructure is formed with dynamically recrystallized equiaxial alpha and beta grains and beta regions with alpha phase of acicular and laminar types, which is related to the temperature gradient of the stir zone during FSP. It has been established that, with increase in the number of FSP passes to three, there is an increase in ultimate strength (up to 1173 MPa) and wear resistance (by 33%). Improvement of the ultimate strength after three passes of FSP is dictated by a decrease in grain size in the stir zone by 88% in comparison with the initial Ti6Al4V alloy. It has been demonstrated that, after four passes of FSP in the stir zone, an increase in the gain size and a decrease in the ultimate strength to 686 MPa occur, which is related to formation of coarse defects along the contours of metal flows. At the same time, the wear resistance of Ti6Al4V alloy after four passes of FSP increases by 39% in comparison with the initial material.