The formation of precipitates and their effect on mechanical properties and irradiation damage in V–4Cr–4Ti alloys have been investigated using transmission electron microscope, high-temperature tensile tests and high-voltage electron microscope (HVEM). V–4Cr–4Ti alloys were aged for 20–40 h at 873 K, and extremely fine precipitates were produced during the aging process, which coarsened with aging time. The results of high-temperature (773, 873 and 973 K) tensile tests showed an increase in strength with increasing aging time (i.e., increasing size of precipitates) while a decrease in the uniform elongation. There was evidence that presence of precipitates strengthened V–4Cr–4Ti alloys. In situ HVEM observations showed that the precipitates restricted the growth rate of dislocation loops induced during electron irradiation at 773 K. The interactions between precipitates and irradiation-induced dislocation loops were discussed. The presence of particles alleviated the increase in irradiation hardening up to an irradiation dose of 3.42 dpa (displacement per atom). The precipitates shrank in size during electron irradiation, which was due to the dissolution of constituent atoms of the precipitates into the alloy matrix.