Deep infection is a serious and costly complication of total knee arthroplasty (TKA), which can increase patient morbidity and compromise functional outcome and satisfaction. Two-stage revision with an interval of parental antibiotics has been shown to be the most successful treatment in eradicating deep infection following TKA. We report a large series by a single surgeon with a highly specialized revision TKA referral practice. We identified 84 patients treated by a two-stage revision. We defined "successful two-stage revision" as negative intraoperative cultures and no further infection-related procedure. We defined "eradication of infection" on the basis of negative cultures and clinical diagnosis. After a mean follow up of 25 months, eradication of the infection was documented in 90.5% of the patients; some had undergone further surgical intervention after the index two-stage procedure. Successful two-stage revision (e.g. no I&D, fusion, amputation) was documented only in 63.5% of the patients. We also observed a trend between presence of resistant staphylococcus (MRSA) (p=0.05) as well as pre-revision surgical procedures (p=0.08) and a lower likelihood of successfully two-stage revision. Factors affecting the high failure rate included multiple surgeries prior to the two-stage revision done at our institution, and high prevalence of MRSA present among failed cases. The relatively high rate of failure to achieve a successful two-stage revision observed in our series may be attributed to the highly specialized referral practice. Thus increasing the prevalence of patients with previous failed attempts at infection eradication and delayed care as well as more fragile and immune compromised hosts.