[2] In October 1817, he went to Paris to complete his medical studies, specialising in anatomy and investigating cerebral morphology under Spurzheim's supervision in 1818–19.

This memorable discussion, inspired by one of Andrew Combe's essays, took place at the Royal Medical Society on 21 and 25 November 1823, and lasted till nearly four in the morning.

The essay was published in the Phrenological Journal (vol 1, p. 337); but records of the discussion were suppressed by means of an injunction obtained by the Medical Society from the Court of Session.

His practice grew quickly because of Combe's personal qualities – his ability to listen, and his exceptional professional courtesy.

Early in 1836 he received the appointment of physician to King Leopold I of Belgium (with Dr James Clark's recommendation) and moved to Brussels; but his health again failed, and he returned to Edinburgh in the same year.

Two winters in Madeira and a voyage to the United States failed to improve things, and he died while on a visit to a nephew at Gorgie Mills, on the south-west side of Edinburgh, on 9 August 1847.

The grave is located on the south side of the "Bairn's Knowe" behind the older stones, and backing onto the former church halls.

In his book The Physiology of Digestion he commented that "the arguments of Mr Graham and Dr Alcott in favour of exclusive vegetable diet, are not based on sound physiological principles, and the broad assertions which they make of the superior strength of vegetable-eating savages in comparison with civilised Europeans, rest on insufficient evidence, and are not supported by the experience of trustworthy observers.