We examined gene models for two traits with and without antagonistic pleiotropy using a locus-based simulation model to investigate the effects of different population sizes, heritabilities and economic weights, using index selection, and index selection with optimum selection (OS), over 10 generations. Gene models included additive and dominance gene action, with equal and varying initial allele frequencies with and without pleiotropy for a fixed level of resources (i.e. founder sizes each generation of 40, 80 and 160 with progeny arrays that totaled 800 per generation). Pleiotropy (with an initial r g of −0.5), reduced gain by~8-10% when heritabilities for both traits were the same (0.2), relative to non-pleiotropic cases. When traits had different heritabilities (i.e. 0.2 and 0.4), gains in the lower heritability trait were substantially lower, especially with pleiotropy present. In general, OS with slightly larger population sizes could offset losses in gain, but rarely overrode the large effects of different heritabilities or economic weights. Pleiotropy increased response variance among traits, which was magnified when heritabilities were different. Identifying an appropriate weight on relatedness in the OS process is important to manage coancestry expectations around the loss of alleles (or fixation of recessive alleles) and to minimise response variance. The dynamics of selection intensity, drift, rate of coancestry build-up, response variance, etc. are complex for multi-trait selection; however, a few economically viable strategies could reduce the adverse effects of selecting against genetic correlations without drastically impairing gain.