Core tip: The presented study used a large primary hospital cohort to test the effect of a commercially available probiotic drink in the prevention of antibiotic-associated diarrhea (AAD) in a decision-based manner. This is the first manufacturer-independent study showing a clear advantage of a probiotic drink containing Lactobacillus casei DN 114001 in AAD prevention. The study additionally contains a calculation of cost-effectiveness and identifies risk factors for AAD. In a second small pilot study, we compared for the first time two commercially available drinks in a head-to-head analysis.