Gyfford was the last Agent of Madras before it was permanently upgraded to a presidency. He had been a member of the Council of Fort St George since 1662. On 21 June 1683 he established the bank of Madras, a forerunner to the State Bank of India. Gyfford made attempts to curb the slave trade in Madras, and cultivated peace with the Sultan of Golconda. From 1684 to 1685, Gyfford was also President of Bengal.

In 1685 Gyfford returned to power as President of Madras, and faced a number of obstacles. He first attempted to impose stricter taxation, which resulted in a rebellion and work boycott. Gyfford threatened to abolish anyone who did not pay taxes, and confiscate their goods. An agreement however was reached in January 1686. Later that year, he also faced a mutiny on behalf of the Company's mercenary Portuguese soldiers, and a famine in Madras that killed 300,000. In the midst of a war between Golconda, allied to Madras, and the Mughal Emperor Aurangzeb, Gyfford was recalled.