Abstract: Here we report the discovery of 2-(4-(3-(trifluoromethoxy)phenoxy)picolinamido)benzo[d]oxazole-5-carboxylate as an antibacterial with potent and selective activity against C. difficile. Its MIC50 and MIC90 values, documented across 101 strains of C. difficile, are 0.12 and 0.25 ?g/mL, respectively. The compound is effective against C. difficile both at the logarithmic (vegetative) and stationary phases of growth. It targets cell-wall biosynthesis, as assessed both by macromolecular biosynthesis assays and by scanning-electron microscopy. Animals infected with a lethal dose of C. difficile and treated with compound 1 had better survival compared to treatment with vancomycin, which is the front-line antibiotic used for severe recurrent C. difficile infection.