In the mechanical alloying (MA) of vanadium alloys, various particles can have a combined dispersion-strengthening effect. The nature, especially the thermal stability, of the dispersion particle agents can play an important role for the strengthening at elevated temperatures. In order to optimize the particle species in dispersion strengthened vanadium alloys for high temperature application, this study focuses on the hardening of V–4Cr–4Ti alloy by different dispersion particle agents such as yttrium compounds and carbides. Alloying degrees, grain sizes, densifications and solid solution of interstitial impurities are compared for better understanding the hardening due to nano-particles. Though the dissolution of carbides may be poor, it has been found that the hardening due to Ti3SiC2 addition is efficient and most stable after annealing at high temperature up to 1723K.