Bovine respiratory disease complex is the most economically significant disease of feedlot cattle. Putative causal organisms include Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma bovis, bovine herpesvirus, bovine viral diarrhea virus, bovine respiratory syncytial virus, and parainfluenza type 3 virus. Although vaccination against the putative causal organisms is a frequently used approach to aid in the prevention of BRD, it is also common and legal for antibiotics to be used for metaphylaxis at the arrival of beef cattle at feedlots. With a more significant concern for prudent antibiotic use in the beef industry, it is essential for decision making with regards BRDC management to understand the efficacy of metaphylaxis as a preventive management practice for BRDC. Systematic reviews of randomized controlled trials yield the highest level of evidence for the efficacy of treatment under field conditions, and comparative efficacy can be examined using network meta-analysis for multiple comparisons. Establishing the efficacy of metaphylaxis for the prevention of BRDC will serve to improve decision makers’ ability to engage in effective stewardship of antibiotics.