Treatment of mycotic aortic aneurysm by excision and extraanatomic bypass is difficult to apply when the infectious process involves the visceral arteries. On the basis of experimental studies in our laboratory that demonstrated prolonged antistaphylococcal activity of rifampin-bonded, gelatin-impregnated Dacron grafts after implantation in the arterial circulation, this conduit was successfully used for in situ replacement of a native aortic infection in two patients. Both patients had fever, leukocytosis, abdominal or back pain, and a computed tomographic scan that demonstrated contained rupture of a mycotic aneurysm. Preoperative computed tomography-guided aspiration and culture of periaortic fluid from one patient grew Staphylococcus aureus. Treatment consisted of prolonged (6 weeks) culture-specific parenteral antibiotic therapy, excision of involved aorta, oxychlorosene irrigation of the aortic bed, and restoration of aortic continuity by in situ prosthetic replacement. A preliminary right axillobifemoral bypass was performed in the patient who had an infection involving the suprarenal and infrarenal aorta. In both patients intraoperative culture of aorta wall recovered S. aureus. Patients were discharged at 20 and 21 days. Clinical follow-up and computed tomographic imaging of the replacement graft beyond 10 months after surgery demonstrated no signs of residual aortic infection. In the absence of gross pus and frank sepsis, the use of an antibiotic-bonded prosthetic graft: with antistaphylococcal activity should be considered in patients who have arterial infections caused by S. aureus when excision and ex situ bypass are not feasible.