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We studied whether computer-assisted surgery could properly align total knee arthroplasty when traditional instrumentation was not possible or appropriate. We identified 16 patients (18 knees) who we believed could not be treated using traditional instrumentation because of posttraumatic femoral deformity, retained femoral hardware, a history of osteomyelitis, or severe cardiopulmonary disease. Computer-assisted surgery was successfully used in 17 knees; we were unable to accurately register the hip in one morbidly obese patient. We judged the overall mechanical axis of the limb using computer-assisted surgery acceptable in 16 of 17 knees. One patient with a major posttraumatic biplane deformity had an overall mechanical axis in 4 degrees of varus. Computer-assisted navigation seemed helpful in difficult situations where accurate alignment remains crucial, yet traditional instrumentation is not applicable.