Alfalfa (Medicago sativa L.) yield is severely compromised by soil salinity, especially at the level of seedling establishment. This question was addressed by proteomics to decipher whether specific changes in protein accumulation correlate with germination performance of alfalfa seeds submitted to a salinity stress as obtained by imbibing seeds in the presence of NaCl. This study used alfalfa seeds submitted to an osmopriming invigoration treatment that proved very efficient in counteracting the negative effect of salinity stress on germination performance. Comparative proteomic analyses disclosed 94 proteins commonly characterizing the response of both the untreated control and osmoprimed seeds to the experimental salinity stress. Remarkably, many of them, representing 84 proteins, showed contrasting accumulation patterns when comparing the untreated control and osmoprimed seeds submitted to the same salt stress. Thus numerous changes observed in the proteome of the untreated control seeds imbibed in the presence of salt, and presumably accounting for the loss in seed vigour associated with salinity stress, can be substantially reversed in osmoprimed seeds undergoing this stress. These data therefore provide a biochemical understanding of the increase in seed vigour generally observed with primed seeds.