In 1854, Sayre performed his first operation for the cure of hip ankylosis, which involved removal of part of the femur (at its head) to facilitate movements of the hindered joint. It was the first successful operation of its kind in the US. In 1871 he made a tour in Europe, and by invitation gave demonstrations of his methods before numerous medical societies. Five years later he was a delegate to the International Medical Congress at Philadelphia, and performed before that body an operation for hip disease. Joseph Lister, the founder of antiseptic surgery, was quoted as saying, "I feel that this demonstration would of itself have been a sufficient reward for my voyage across the Atlantic." The next year, 1877, he was sent by the American Medical Association to the meeting of the British Medical Association at Manchester, where he demonstrated his new treatment of diseases and deformities of the spine by suspension and the application of plaster-of-Paris bandages. Demonstrations were repeated at principal hospitals throughout England. Sayre was a voluminous writer, chiefly on topics related to surgery. He invented many instruments for use in operations and for the relief of deformities. Sayre was consulting surgeon to St Elizabeth's Hospital, the Northwestern Dispensary, and the Home for the Incurables in New York. He was an honorary member of leading American and European societies. In 1972, in recognition of his work, the King of Sweden made him a Knight of the Order of Vasa. While mostly hailed, the methods introduced by Sayre were also criticized by colleagues. The hip-joint operation introduced by Sayre proved to be technically challenging. In the first few decades after its introduction, about half of the patients died after the operation and only some of those who recovered regained flexibility. Therefore, it was often avoided in favor of non-surgical treatment. Some doctors (e.g. Newton Melman Shaffer) criticized the use of plaster-of-Paris advocated by Sayre, and found it unsuitable for treating Pott disease. In 1849, Sayre married Eliza Ann Hall (January 19, 1822 – January 7, 1894), a painter from a family of artists. They had three sons and a daughter. All three sons became doctors, working with their father, but two of them died in middle age: Charles Henry Hall Sayre (1850–1880) from a fall, and Lewis Hall Sayre (1851–1890) from heart disease. His daughter Mary Jane never married and lived with the family, helping her father with his publications.