At the time of independence there were only thirty medical colleges in India and it was getting increasingly difficult to get admission in the colleges. The Travancore Cochin Medical Council, which started functioning from 1944, and the Senate of the Travancore University decided to start a Medical College at Thiruvananthapuram.

In April 1948, Government formed a committee, to prepare a project proposal to start the college. The special Officer of the Project, Dr. Karunakaran submitted the report within one month. The foundation stone of the college was laid on 26th January 1950 by His Highness Rajapramukh Padmanabhadasa Balarama Varma. Pandit Jawaharlal Nehru inaugurated the Medical College . The first batch consists of sixty students. Pandit Jawaharlal Nehru also inaugurated the Medical College Hospital on 8th February 1954.