Vanadium-48 was produced through the irradiation of the natural titanium target via the natTi(p, xn)48V reaction. The titanium target was irradiated at 1 mA current and by a 21 MeV proton beam for 4 hours. In this paper, the activity of 48V, 43Sc, and 46Sc radionuclides and the efficacy of the 47Ti(p, g), 48Ti(p, n), and 49Ti(p, 2n) channel reactions to form 48V radionuclide were determined using MCNPX code. Furthermore, the experimental activity of 48V was compared with the estimated value for the thick target yield produced in the irradiation time according to MCNPX code. Good agreement between production yield of the 48V and the simulation yield was observed. In conclusion, MCNPX code can be used for the estimation of the production yield