Probiotics may not prevent antibiotic-associated diarrhea (AAD), including Clostridium difficile infections. That was the finding of a randomized, double-blind, placebo-controlled trial in nearly 3000 inpatients aged ≥65 years who were exposed to one or more oral or parenteral antibiotics. Patients were randomized to a multistrain preparation of lactobacilli and bifidobacteria or placebo for 21 days. The rate of AAD was 10.8% in the probiotic group and 10.4% in the placebo group (P = 0.71). C. difficile was uncommon and occurred in 0.8% of the probiotic group and 1.2% of the placebo group (P = 0.35). The authors state that “we identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in the prevention of AAD or CDD.” (Lancet published online August 8, 2013. doi: 10.1016/S0140-6736(13)61218-0). An accompanying editorial wonders if this study can tip the balance of probiotic evidence, as it was a rigorously performed study vs previous small studies showing a positive effect. But, the current study used only two types of non-pathogenic bacteria (doi: 10.1016/S0140-6736(13)61571-8). Still, the cost effectiveness of routine probiotic use must be questioned based on this study.