The weldability, microstructures, and mechanical properties of two L12-nanoparticle-strengthened medium-entropy alloys (MEAs) Ni43.4Co25.3Cr25.3Al3Ti3 and Ni42.4Co24.3Cr24.3Al3Ti3V3 (at.%) are explored after electron beam welding (EBW). Strong yet ductile defect-free joints were produced with coarse columnar grains (118–245 μm) in the fusion zones, which were larger than the equiaxed grains in the heat-affected zones (15.6–22.3 μm) and in the base materials (4.6–5.6 μm). Both EBWed MEAs showed high yield strengths (838–858 MPa), high ultimate tensile strengths (1416–1420 MPa), and good fracture strains of 20–21 % at 77 K, which are 66∼83 %, 84–89 %, and 57–81 %, respectively, of those of the respective thermo-mechanically treated (TMT) MEAs. The V-doping improved the cryogenic mechanical properties of the TMT MEA while not influencing those of the EBWed MEA. High back-stress hardening contributes to over 50 % of the cryogenic strength. Both EBWed MEAs exhibited abundant dislocation networks, stacking faults, and nanoscale deformation twins after fracture, producing a high strain hardening rate and good ductility.