We conducted a 10-yr study to establish whether chronic wasting disease (CWD) was readily transmissible to domestic cattle (Bos taurus) following oral inoculation or by cohousing cattle with captive cervids in outdoor research facilities where CWD was enzootic. Calves (n=12) were challenged orally on one occasion using brain homogenate derived from CWD-infected mule deer (Odocoileus hemionus). Five uninoculated cattle served as unchallenged controls. Two other groups of cattle (n=10–11/group) were housed outdoors for 10 yr in captive cervid research facilities. The environmentally challenged cattle were exposed to CWD-associated prions through common paddocks, feed, and water and via direct daily contact with known and potentially infected mule deer or wapiti (Cervus canadensis) throughout the decade-long study period. None of the exposed cattle developed neurologic disease during the study. We euthanized cattle surviving to 10 yr postchallenge and examined all for lesions or disease-associated prion protein (PrP^d) by histopathology, immunohistochemistry, and western immunoblot analysis of central nervous system and lymphoid tissue. None had evidence of PrP^d accumulation. We conclude that the risks of CWD transmission to cattle following oral inoculation or after prolonged exposure to contaminated environments are low.