Background: In pig and poultry breeding, the objective is to improve the performance of crossbred production animals, while selection takes place in the purebred parent lines. One way to achieve this is to use genomic prediction with a crossbred reference population. A crossbred reference population benefits from expressing the breeding goal trait but suffers from a lower genetic relatedness with the purebred selection candidates than a purebred reference population. Our aim was to investigate the benefit of using a crossbred reference population for genomic prediction of crossbred performance for: (1) different levels of relatedness between the crossbred reference population and purebred selection candidates, (2) different levels of the purebred-crossbred correlation, and (3) different reference population sizes. We simulated a crossbred breeding program with 0, 1 or 2 multiplication steps to generate the crossbreds, and compared the accuracy of genomic prediction of crossbred performance in one generation using either a purebred or a crossbred reference population. For each scenario, we investigated the empirical accuracy based on simulation and the predicted accuracy based on the estimated effective number of independent chromosome segments between the reference animals and selection candidates. Results: When the purebred-crossbred correlation was 0.75, the accuracy was highest for a two-way crossbred reference population but similar for purebred and four-way crossbred reference populations, for all reference population sizes. When the purebred-crossbred correlation was 0.5, a purebred reference population always resulted in the lowest accuracy. Among the different crossbred reference populations, the accuracy was slightly lower when more multiplication steps were used to create the crossbreds. In general, the benefit of crossbred reference populations increased when the size of the reference population increased. All predicted accuracies overestimated their corresponding empirical accuracies, but the different scenarios were ranked accurately when the reference population was large. Conclusions: The benefit of a crossbred reference population becomes larger when the crossbred population is more related to the purebred selection candidates, when the purebred-crossbred correlation is lower, and when the reference population is larger. The purebred-crossbred correlation and reference population size interact with each other with respect to their impact on the accuracy of genomic estimated breeding values.