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The Government of Travancore in 1948 appointed a committee to formulate proposals for starting a Medical College at Trivandrum. The Committee submitted its report and the scheme was sanctioned in October 1948. Dr. C.O. Karunakaran was appointed Special Officer for the implementation of the scheme.

The College Campus has 139 acres (0.56 km2) of picturesque land with a number of hillocks surrounded by evergreen coconut groves and paddy fields, facing the sea which lies at a distance of three kilometres, and is located on the North – West border of the Trivandrum city. The College, is linked with the different sections of the city by bus routes, is very near the national highway NH 47 and the nearest railway station is just few kilometres from the college. The topographical layout and the architectural designs were prepared by Mr. J.A. Ritchie from Bombay. The College and the hospital buildings are separated by playgrounds for football, hockey, a cricket pitch, courts for tennis, basketball, badminton and volleyball and a 400 meter track.

The foundation stone of the College was laid by His Highness the Raja Pramuk of Travancore – Cochin at 11:45 AM on 26-01-1950. The first batch of students was admitted in August 1951. The College was formally inaugurated by Shri. Jawaharlal Nehru at 8:00 AM on 27th Nov. 1951. In January 1952, the Sri. Avittom Thirunal Hospital ( SATH ) was inaugurated by Smt. Rajkumari Amrit Kaur. In 1952, men's hostel and 1year later women's hostel was also inaugurated. The Medical College Hospital was inaugurated by Shri. Jawaharlal Nehru on 1954.

The School of Nursing http://www.contvm.org  was inaugurated by Her Highness Sethu Lakshmi Bai in 1954 and upgraded to College of Nursing in 1963. The Cancer block was inaugurated in 1958 and later after two decades the Regional Cancer Centre(http://www.rcctvm.org/), one of the premier cancer care centers in South India was established. The Dentistry course and the first post-graduate course commenced in 1959.

The sixties saw the establishment of library. The limb center, Mental hospital and Ophthalmic hospital were brought under Medical College administration. Later in nineties the Regional Institute of Ophthalmology(http://www.riotrivandrum.org/) came into existence. Over the years, the campus saw establishment of Sree Chitra Thirunal Centre, College of Pharmaceutical Sciences, Priya Darsini Institute of Paramedical Sciences, Silver Jubilee Auditorium and the Various hostels. The institution has thus grown to glorious proportions.

It is financed and administrated by Health and Family welfare Dept http://www.kerala.gov.in/dept_health/health.htm Govt. of Kerala. The Medical College is affiliated to the University of Kerala.. Trivandrum Medical College is the first medical college in Kerala. The college started with an annual admission of 60 students, which was increased to 200 in 1983. Now it is ranked among the top 20 medical colleges in the country.

A super-specialty block with state-of-the-art technology and modern equipments, exclusively housing all the medical and surgical super-specialties of the college, has been completed and has started functioning as the OP block of the super-specialties from July 1, 2010. It was funded under the Prime Minister's Swasthya Bheema Yojna scheme and by the State government. The 253-bed SS block, spread over 160,000 sq ft (15,000 m2) on seven floors, houses the outpatient clinics and inpatient wards of the six super specialties, eight operation theatres, 29-bed six intensive care units, haemo dialysis unit and renal transplant unit, apart from administrative blocks. Full fledged functioning of the complex will commence after its proposed dedication to the nation by the Prime Minister. 

A newly constructed out-patient block for the broad specialties has also been opened to the public