OBJECTIVES: To develop a model which calculates economic consequences of treatment of cattle at high risk of developing Bovine Respiratory Disease (BRD high-risk cattle), the most common and economically detrimental cattle disease in US feedlots. The model had to be easily adaptable to clinical variations and regional and timely changes in cost data. METHODS: A decision tree was developed in MS Excel evaluating the consequences of initial treatment of BRD high-risk cattle with tulathromycin, florfenicol, and tilmicosin on total costs and losses associated with BRD and its treatments over an entire feeding period. Clinical data were derived from 5 comparative trials considering success rate of initial treatment of BRD high-risk cattle, occurrence and outcome of subsequent BRD outbreaks, chronic cases, and mortalities. The model allows the estimation of results separately according to outcomes of one of the 5 clinical trials. Cost parameters included cattle purchase, treatment costs (first and re-treatments), costs of chronic and dead cows (perspective of the producer). RESULTS: Considering cost data derived from multiple sources as of 2010, total costs over the entire feeding period associated with first and subsequent BRD treatments were lowest with tulathromycin, regardless of the study selected as basis for efficacy data. Total treatment costs for one cattle ranged from $27.78 to $54.38 (tulathromycin), $52.83 to $84.06 (florfenicol), and $41.35 to $141.13 (tilmicosin), and cost savings with tulathromycin were calculated between $19.65 and $43.59 (vs. florfenicol) and $9.77 and $86.75 (vs. tilmicosin), depending on the clinical trial considered as basis for efficacy data. Savings with tulathromycin were attributed to fewer BRD treatments, less chronics and mortalities. CONCLUSIONS: The model allows the estimation of total costs of treatment of BRD high-risk cattle considering various clinical outcomes as reported in 5 trials, being easily adaptable to high variability of cost and income data in livestock.