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Percutaneous anchoring of femoral amputation prostheses using osseointegrating titanium implants has been in use for more than 25 years. The method offers considerable advantages in daily life compared with conventional socket prostheses, however long-term success might be jeopardized by implant-associated infection, especially osteomyelitis, but the long-term risk of this complication is unknown.(1) To quantify the risk of osteomyelitis, (2) to characterize the clinical effect of osteomyelitis (including risk of implant extraction and impairments to function), and (3) to determine whether common patient factors (age, sex, body weight, diabetes, and implant component replacements) are associated with osteomyelitis in patients with transfemoral amputations treated with osseointegrated titanium implants.We retrospectively analyzed our first 96 patients receiving femoral implants (102 implants; mean implant time, 95 months) treated at our center between 1990 and 2010 for osteomyelitis. Six patients were lost to followup. The reason for amputation was tumor, trauma, or ischemia in 97 limbs and infection in five. All patients were referred from other orthopaedic centers owing to difficulty with use or to be fitted with socket prostheses. If found ineligible for this implant procedure no other treatment was offered at our center. Osteomyelitis was diagnosed by medical chart review of clinical signs, tissue culture results, and plain radiographic findings. Proportion of daily prosthetic use when osteomyelitis was diagnosed was semiquantitatively graded as 1 to 3. Survivorship free from implant- associated osteomyelitis and extraction attributable to osteomyelitis respectively was calculated using the Kaplan-Meier estimator. Indication for extraction was infection not responsive to conservative treatment with or without minor débridement or loosening of implant.Implant-associated osteomyelitis was diagnosed in 16 patients corresponding to a 10-year cumulative risk of 20% (95% CI 0.12-0.33). Ten implants were extracted owing to osteomyelitis, with a 10-year cumulative risk of 9% (95% CI 0.04-0.20). Prosthetic use was temporarily impaired in four of the six patients with infection who did not undergo implant extraction. With the numbers available, we did not identify any association between age, BMI, or diabetes with osteomyelitis; however, this study was underpowered on this endpoint.The increased risk of infection with time calls for numerous measures. First, patients should be made aware of the long-term risks, and the surgical team should have a heightened suspicion in patients with method-specific presentation of possible infection. Second, several research questions have been raised. Will the surgical procedure, rehabilitation, and general care standardization since the start of the program result in lower infection rates? Will improved diagnostics and early treatment resolve infection and prevent subsequent extraction? Although not supported in this study, it is important to know if most infections arise as continuous bacterial invasion from the skin and implant interface and if so, how this can be prevented?Level IV, therapeutic study.