The effects of bacitracin methylene disalicylate (BMD) and scours on the fecal microbiome, animal performance, and health were studied in Holstein bull calves. Holstein bull calves (n = 150) were obtained from a single source at 12 to 24 h of age. Bull calves were randomly assigned to 1 of 2 treatments including CON (no BMD; n = 75 calves) and BMD (n = 75 calves). Starting 3 d after arrival, BMD was added into milk replacer (0.5 g/feeding; twice daily) and fed to the calves for 10 consecutive d. No differences (P > 0.10) were observed in ADG for d 0 to 28 and d 0 to 56, DMI for d 0 to 28, d 29 to 56, and d 0 to 56, or G:F for d 0 to 28, d 29 to 56, and d 0 to 56; ADG for d 29 to 56 tended to increase (P < 0.10) for BMD-treated calves compared with controls. Fecal samples were collected from 15 scouring calves and 10 cohorts (nonscouring calves received on the same day and administered the same treatment as the scouring calves). Animal morbidity and fecal score did not vary between the 2 treatments. Mortality was not influenced by the treatments in the BMD administration period or throughout the experiment. Fecal samples were subjected to pyrotagged 454 FLX pyrosequencing of 16S rRNA gene amplicon to examine compositional dynamics of fecal microbes. Escherichia, Enterococcus, and Shigella had greater (P < 0.05) populations in the BMD group whereas Dorea, Roseburia, Fecalibacterium, Papillibacter, Collinsella, Eubacterium, Peptostreptococcus, and Prevotella were decreased (P < 0.05) by BMD treatment. Genus populations were also compared between scouring and nonscouring calves. Streptococcus was the only genus that had notable increase (P < 0.05) in fecal samples from scouring calves whereas populations of Bacteroides, Roseburia, and Eubacterium were markedly (P < 0.05) greater in nonscouring calves. These results show that BMD has the ability to alter the composition of the fecal microbiome but failed to improve performance in Holstein bull calves. Discrepancy of microorganism profiles between scouring and nonscouring calves might be associated with the occurrence of scours and bacterial genera identified might be potential target of treating diarrhea.