Staphylococcus aureusis a common colonizer of the human gut and in doing so it must be able to resist the actions of the host’s innate defences. Bile salts are a class of molecules that possess potent antibacterial activity that control growth. Bacteria that colonize and survive in that niche must be able to resist the action of bile salts, but the mechanisms by whichS. aureusdoes so are poorly understood. Here we show that FadB is a bile-induced oxidoreductase which mediates bile salt resistance and when heterologously expressed inEscherichia colirenders them resistant. Deletion offadBattenuated survival ofS. aureusin a model of the human distal colon.