He was greatly influenced by Joseph, Lord Lister (1827–1912), who revolutionised surgery by developing antisepsis, by the use of phenol, thus decreasing drastically the enormous mortality of surgical patients due to infections.

He was knighted in the 1902 Coronation Honours for services to medicine,[4] receiving the accolade from King Edward VII at Buckingham Palace on 24 October that year.

Macewen was its first chief surgeon and with the help of engineers and workers at the nearby Yarrow Shipbuilders he designed the Erskine artificial limb.

[3] He lived at Garrochty on the Isle of Bute until his death and was buried nearby in the churchyard of St Blane's Church at Kingarth.

On the basis of these signs Macewen thought that there was good evidence of an "irritation to the lower and middle portions of the ascending convolutions…in the left frontal lobe".

According to one of his biographers, "his thorough knowledge of the natural history of pyogenic diseases of the temporal bone and nasal sinuses, in addition to his clear description of cranial anatomy, as illustrated in his Atlas of Head Sections, were especially important in developing his successful treatment of brain abscess.

One of his earliest contributions while at the Royal Infirmary, in 1877, was in orthopaedics, by means of the development of the first bone grafts, but also in knee surgery using a special instrument (Macewen's osteotome) both techniques becoming key treatments for the highly prevalent disease of rickets (caused by a lack of Vitamin D).

[7] As part of the late 1970s redevelopment of Glasgow Royal Infirmary, where Macewen spent most of his career, a new laboratory block was named in his honour.