The objective of this study was to determine the effect of feeding direct-fed microbials (DFM) on the growth performance and prophylaxis of calf diarrhea during the pre-weaning period as an alternative to antibiotics. A multi-species DFM was formulated including three lactic acid bacteria (Lactobacillus salivarius Ls29, Pediococcus acidilactia Pa175, and L. plantarum Lp177), three Bacillus strains (B. subtilis T4, B. polymyxa T1 and SM2), one yeast, Saccharomyces boulardii, and a nonpathogenic E. coli Nissle 1917. Lactic acid bacteria and Bacillus strains were selected based on the antibacterial activity against various animal pathogens, especially pathogenic E. coli using agar diffusion methods in vitro. Test and control groups were fed milk replacer and calf starter supplemented with DFM ($10^9$ cfu each of eight species/d/head, n = 29) or with antibiotics (0.1% neomycin sulfate in milk replacer and Colistin 0.08% and Oxyneo 110/110 0.1% in calf starter, n = 15), respectively. Overall fecal score and the incidence rate of diarrhea were reduced in the DFM group compared to the antibiotics one. About 40% of calves in antibiotic group suffered from diarrhea while in DFM group only 14% showed diarrhea. There was no difference in the average daily gain and feed efficiency of two groups. The hematological levels of calves were all within the normal range with no significant difference. In conclusion, the feeding of multispecies DFM during the pre-weaning period could reduce calf diarrhea and there was no difference in the growth performance between the groups, thus showing the potential as an alternative to antibiotics.