When considering an elk (Cervus elaphus) restoration program, wildlife managers must evaluate the positive and negative elements of translocation. We prepared this protocol to give an overview of health considerations associated with translocation of elk, with an emphasis on movement of free-ranging elk from western North America to the southeastern USA. We evaluated infectious agents and ectoparasites reported in elk from two perspectives. First, we made a qualitative estimate of the ability of the agent to be introduced and to become established. This was done using a selected set of epidemiologic factors. Second, if there was a good possibility that the organism could become established in the release area, the potential pathological consequences for elk and other wildlife, domestic animals, and humans were assessed via examination of the literature and consultation with other animal health specialists. The results of these evaluations were used to classify infectious agents and ectoparasites as low risk (n = 174), unknown risk (n = 10), and high risk (n = 9). We classified Anaplasma marginale, Anaplasma ovis, Mycobacterium paratuberculosis, Pasteurella multocida serotype 3, Elaphostrongylus cervi, Dicrocoelium dendriticum, Fascioloides magna, Echinococcus granulosus, Dermacentor albipictus, and Otobius megnini as unknown risks. High risk infectious agents and ectoparasites were the agent of chronic wasting disease, Brucella abortus, Mycobacterium bovis, Dermacentor andersoni, Ixodes pacificus, and Psoroptes sp. Parelaphostrongylus tenuis, Elaeophora schneideri, and a Babesia sp. are parasites endemic in the southeastern USA that may present a “reverse risk” and adversely affect elk if released in some parts of the region. We developed a five-component protocol to reduce the risk of introduction of high risk infectious agents and ectoparasites that included: (1) evaluation of the health status of source populations, (2) quarantines, (3) physical examination and diagnostic testing, (4) restrictions on translocation of animals from certain geographic areas or populations, and (5) prophylactic treatment.