Although low levels of vanadium-doping can enhance the friction stress and strength of L12-nanoparticles strengthened medium-entropy alloys (MEA), how high concentrations of vanadium affect the weldability, microstructure, mechanical properties, and fracture behavior remains unknown. In this work, we designed a vanadium-doped, L12-nanoparticle-strengthened MEA Ni41.4Co23.3Cr23.3Al3Ti3V6 (at.%), which showed a high fracture toughness of 238 MPa × m1/2, a high friction stress of 410 MPa, and a Hall-Petch strengthening coefficient of 782 MPa × μm1/2. Pieces of the HEA were joined using electron-beam welding (EBW). Strong yet ductile defect-free joints were produced which had coarse columnar grains (88 μm) with a {110}<001> texture in the fusion zone, which was larger than the equiaxed grains in the heat-affected zones (14.9 μm) which had strong {110}<001> and relatively weak {110}<112> texture. In contrast, the base materials had fine grains (2.2 μm) with a strong {110}<111> and a relatively weak {110}<112> texture. The EBWed MEA showed a high yield strength of 599 MPa, a high ultimate tensile strength of 939 MPa, a good fracture strain of 20 %, and a fracture toughness of 198 MPa × m1/2, which were 75 %, 83 %, 58 %, and 83 %, respectively, of the values of for the thermo-mechanically treated counterpart. The reduced strength arose from the coarse columnar grains, while the reduced fracture strain and fracture toughness could be ascribed to the reduced deformation twinning and the absence of annealing twins, which produced a poor strain hardening capability. The EBWed MEA exhibited abundant dislocation networks, indicating that a high concentration of vanadium inhibited the occurrence of stacking faults and nanoscale deformation twins.