Born at Millmount, Kilkenny he attended Kilkenny College and in 1790 began studying Arts at Trinity College, Dublin. At the same time he was accepted as an apprentice to Philip Woodroffe, a surgeon at the Dr. Steevens' Hospital, Dublin. In 1795 he was promoted to Bachelor of Arts at Trinity College, and in the same year received his diploma from the Royal College of Surgeons in Dublin. He then went to Edinburgh to complete his medical studies. In June 1797 Colles received his MD - Doctor of Medicine. He returned to Dublin the same year, became first physician at the Meath Hospital and started teaching anatomy and surgery. In 1799 he was elected to the Royal College of Surgeons and succeeded his old teacher, Philip Woodroffe, as resident surgeon to the Dr Steevens' Hospital. He was also co-director of the Cow Pox Institution. He remained with Dr. Stevens’ Hospital until 1841. In 1804 he was appointed professor of both anatomy/physiology and surgery. at the Royal College of Surgeons (Ireland), to which he was later elected president in 1802, at the age of only 29 years, and again in 1830. A competent lecturer and pedagogue, he contributed to making his college one of the most respected in Europe for a couple of decades. When offered knighthood as a baronet in 1839, he declined. When he resigned in 1836, after 32 years in the chair of surgery, failing health was the chief cause. Despite the fact that he suffered from heart failure during his last years, he continued practicing until his death in 1843. He took a great interest in anatomy and spent much of his time in the dissection room. His anatomical discoveries were not epoch-making, but they still bear his name - Colles' ligament and Colles' fascia. He was also a great innovator in topographical anatomy, and concerned himself with the treatment of club foot, publishing his discoveries on this subject in 1818.