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In this large-pen commercial field trial, mixed beef-breed bulls and heifers were randomly allocated at feedlot arrival to 1 of 2 experimental groups: ENRO or TULA. Animals in the ENRO group (10 multi-pen lots; 2037 animals) received a subcutaneous injection of enrofloxacin at a dosage of 3.4 mg/lb (7.5 mg/kg) body weight once at allocation. Animals in the TULA group (10 multi-pen lots; 2036 animals) received a subcutaneous in­jection of tulathromycin at a dosage of 1.1 mg/lb (2.5 mg/kg) body weight once at allocation. Study animals were housed by experimental group in commercial feedlot pens and fol­lowed from allocation until slaughter. There were no statisti­cal differences detected in any of the animal health or feedlot performance outcome variables between the experimental groups at the P < 0.050 level. Given the lack of detectable sta­tistical differences in animal health and feedlot performance outcome variables in the current study, the relative cost effec­tiveness of metaphylaxis programs utilizing enrofloxacin or tulathromycin in mixed beef-breed bulls and heifers at high risk of developing bovine respiratory disease should be depen­dent on the relative cost of each program, as well as any intan­gible attributes such as syringability, storage requirements, potential for antimicrobial resistance, etc.