Infection is a devastating complication following total knee replacement (TKR). In the majority of cases, single- or two-stage revision has excellent results in eradicating infection and restoring function. Rarely, recurrent infection requires alternative treatments such as resection, amputation, or arthrodesis. A review of infections following TKR treated at two joint replacement centers identified 29 cases of resistant knee sepsis treated with a long intramedullary fusion nail. Clinical outcome and radiographs were reviewed at an average follow-up of 48 months (13-114). After the initial intramedullary arthrodesis union occurred in 24 of 29 patients (83%). The average time to fusion was 6 months (3-18 months). Failures included two cases of nail breakage, one of which subsequently achieved fusion following revision nailing, and three cases of recurrent infection requiring nail removal and permanent resection. At a minimum 2-year follow-up, 28% of the patients that achieved fusion complained of pain in the fused knee, 28% complained of ipsilateral hip pain, and two patients complained of contralateral knee pain. Four of the 25 fused patients (16%) remained nonambulatory after fusion, 17 required walking aids (68%) and only four ambulated unassisted. There was no association between age, number of previous procedures, the use of two-stage versus single stage technique, or infecting organism and failure of arthrodesis. Intramedullary arthrodesis is a viable treatment for refractory infection after TKR. Patients undergoing fusion should be informed of the potential for nonunion, recurrence of infection, pain in the ipsilateral extremity, and the long-term need for walking aids.