The Government of Tamilnadu established the Tirunelveli Medical College in 1965, with the agreement of the University of Madras. A total of 75 students were admitted for the MBBS course for the academic year 1965-66 and they had their first year of study at the St Xaviers College for Men and Sarah Tucker College for Women.
In July 1966, the first batch of second year MBBS students started attending the classes in the then newly constructed Anatomy Block. Other departments like Pharmacology, Pathology, Microbiology and Social & Preventive Medicine started functioning in the subsequent years, and the District Headquarters Hospital was converted to Tirunelveli Medical College Hospital.
The college was affiliated to the Madurai Kamaraj University consequent to its inception in 1967 till the newly formed The Tamil Nadu Dr. MGR Medical University in 1988.
The college increased the number of admissions to 100 per year during 1973-74 and was subsequently recognised by the Medical Council of Indiasince the year 1977.
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