The irradiation induced microstructure evolution of S-ferrite in an austenitic stainless steel weld was investigated. To simulate long-term service in light water reactor (LWR) at operating temperature, accelerated thermal aging at 400 degrees C up to 30,000 h was performed. Then, proton irradiation up to 10 displacement per atom (dpa) was subsequently conducted for unaged and aged samples. For the unaged samples, formation of Cr-rich (alpha') phase by spinodal decomposition increased with irradiation dose. Meanwhile, formation of G-phase was promoted after 1 dpa, but decreased after 10 dpa. For the aged samples, after 1 dpa irradiation, Cr-rich (alpha') phase formed by spinodal decomposition during thermal aging was destroyed while population of G-phase increased. After further irradiation up to 10 dpa, alpha' phase was re-precipitated and coarsened significantly, but the degree of which was significantly less compared to the unaged samples. Meanwhile, with increase of irradiation to 10 dpa, G-phase population increased for the aged samples. The difference in the evolution of microstructural features during irradiation were discussed in view of the initial microstructure of S-ferrite.