A prospective, randomized clinical trial among drug abusers was conducted to assess the efficacy and safety of a short course of a combination of a glycopeptide (vancomycin or teicoplanin) and gentamicin compared with a combination of cloxacillin and gentamicin for treatment of right-side endocarditis caused by Staphylococcus aureus. Therapeutic success was significantly more frequent with cloxacillin than with a glycopeptide. No adverse effects were noted among patients in the cloxacillin group. A 14-day course of vancomycin or teicoplanin plus gentamicin is ineffective in this instance because it is associated with a high rate of clinical and microbiological failure.