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Diarrhea is the leading cause of mortality in beef and dairy calves during the first week of life and results in substantial financial loss [1]. Diarrhea is a multifactorial disease and can be infectious or non-infectious. However, in the majority of calves, infectious organisms, especially Cryptosporidium parvum, rotavirus, coronavirus, and E. coli, are the primary cause [2]. The aim of this study was to generate a decision tree, based on prevalence, diagnostic testing and treatment and to estimate associated costs or risk. For each of the four main pathogens, two principal approaches are outlined and compared. The first approach relies on a detailed diagnostic workup and allows for specific etiological treatment. The second approach relies on the trial-and-error method, which involves the use of a first-choice antibiotic, followed by a second- and third-choice antibiotic if the previous ones failed to resolve the disease. In Switzerland, the prevalence of diarrheic calves infected with E. coli is approximately 1% suggesting that the use of antimicrobials for the treatment of scouring calves, in the absence of a diagnostic workup, is not always justified. However, for all four major pathogens, the trial-and-error method affords cheaper treatment compared with treatment based on an etiological diagnosis. This creates a quandary in view of the current worldwide efforts to reduce the use of antibiotics in animal agriculture.