The major histocompatibility complex (MHC) consists of genes involved in immune response and molecular discrimination between self and non-self. MHC genes are the most polymorphic in vertebrates. The origin and maintenance of polymorphism in MHC genes in populations is still unresolved. Mechanisms such as sexual selection and heterozygote advantage have been suggested as explanations for this high variability. In this study, a farmed population of rainbow trout (Oncorhynchus mykiss) characterized by the presence of specific MHC class IIB gene haplotypes at a frequency higher (30%) than that expected from random matings was investigated. Therefore, it was hypothesized that disassortative matings occur with an adaptive advantage for females, resulting in improved reproductive performance when mated with individuals with similar MHC haplotypes. Genetic analyses of the breeders were performed to define the MHC haplotypes and to perform specific matings. The effect of mating was evaluated by analyzing the survival rate of the offspring at various stages of incubation until swim-up. The reproductive performance of the offspring derived from specimens with similar haplotypes showed a better survival trend during the first life stages and reduced malformations. The results obtained are in contrast with the heterozygous advantage theory, therefore it was hypothesized, as for other salmonid species, the presence of a positive selection towards locally adapted MHC genes that promotes reproduction between genetically similar individuals.