Purpose: Complications Of grafts infected with coagulase-negative staphylococci can be eradicated by antibiotic administration, tissue debridement, and in situ graft replacement, but successful treatment may be diminished in a setting of altered immune function. Methods: In a canine model of an established aortic graft infection from Staphylococcus epidermidis, outcomes after in situ replacement were compared between normal dogs and animals made immune-deficient by administration of azathioprine (50 mg/day) and prednisone (10 mg/day). In situ replacement of an infected infrarenal aortic graft with either antibiotic-bonded (silver-ciprofloxacin; Ag-cipro) or conventional polytetrafluoroethylene (PTFE) grafts was performed in 17 control and 18 immune-deficient animals. Results: Four weeks after implantation of a Dacron graft colonized with a biofilm of S. epidermidis, all study animals demonstrated a bacterial biofilm infection with perigraft inflammation or abscess, and in immune-suppressed dogs the incidence of perianastomotic aortitis was increased (p < 0.05). Six weeks after in situ replacement both the Ag-cipro and conventional PTFE grafts were healed without signs of infection in controls, but anatomic evidence of persistent infection and increased S. epidermidis recovery was observed in immune-suppressed animals that underwent in situ replacement of a standard (five of seven) versus antibiotic-bonded (one of 11) PTFE graft (p < 0.006). Overall in situ replacement with an antibiotic-bonded graft yielded a lower frequency of S. epidermidis recovery (two of 19 Ag-cipro graft biofilm with positive culture results versus nine of 16 conventional graft biofilm with positive culture results; (p < 0.003). Conclusions: This study supports the efficacy of in situ replacement for low-grade graft infections caused by S. epidermidis in normal hosts and demonstrates superiority of antibiotic-bonded grafts in immune-deficient hosts.