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Many hearing-impaired patients may significantly benefit from the Hybrid or electro-acoustic stimulation (EAS) cochlear implant (CI). However, as much as 30-55% of CI recipients lose residual hearing after implantation and the potential for associated benefits of EAS over traditional electric-only stimulation. The cause of this post-implantation hearing loss may be immediate or delayed and result from several factors, including surgical trauma, electric stimulation, and the foreign body response. Clinical and post-mortem studies have helped identify factors effecting EAS performance. Animal CI models are an essential translational tool to further investigate these pertinent issues through histopathological investigation with greater control of biological and stimulation variables as well as other unique research tools not available in clinical and post-mortem research. Additionally, animal CI models may provide useful preclinical data for potential therapeutic strategies aimed at improving EAS outcomes. Here we review the parameters required for rigorous study of mechanisms of post-implantation hearing loss, including selection of animal model, hearing loss model, age and sex considerations, surgical technique, and chronic electrical stimulation.