Hepatotoxicity by macrolide antibiotics, particularly erythromycin and derivatives, is a side effect extensively described in the literature. Midecamycin is a semi-synthetic derivative of this family with a wide safety margin of which isolated references of possible secondary hepatobiliary effects have been referred. The present clinical observation describes a case of cholestatic hepatitis which, in our opinion, was related to the administration of diacetyl midecamycin which evolved favorably following discontinuation of the drug. Despite its exceptional frequency and based on the wide therapeutic diffusion of this group of antibiotics, we believe this case to be of interest.