Total knee replacement (TKR) is reserved for patients with severe and disabling arthritis that is non-responsive to conservative measures. Based on existing data, total knee replacement is a safe and cost-effective treatment for alleviating pain and improving physical function in patients who do not respond to conservative therapy. Despite the large variation in health status of patients and types of prosthesis implanted, total knee replacement has proven to be a relatively low risk and successful operation. Each year in the United States surgeons perform approximately 300,000 TKR. Likewise, lower extremity amputation is commonly performed in the United States with an annual incidence of 110,000 per year. Nearly 70% of all lower extremity amputations are performed as the result of chronic vascular disease, followed by trauma (22%), congenital etiology and tumor (4% each). Approximately 50% of all lower extremity amputations are performed secondary to complications from Diabetes Mellitus. Norvell et al. demonstrated that patients who have previously undergone transtibial amputation and ambulate with a prosthesis are more likely to develop degenerative joint disease in the contralateral extremity than the ipsilateral extremity. Further, radiographic changes consistent with osteoporosis have been demonstrated in up to 88% of limbs that have undergone transtibial amputation. To our knowledge, there have been only three reported cases of total knee replacement in patients with ipsilateral transtibial amputation. The purpose of the present study is to review the existing data on total knee replacement in patients who have undergone transtibial amputation. Further we present a patient with a transtibial amputation who underwent contralateral total knee replacement.