72-year-old Padgaonkar, a former editor of The Times of India, was unwell for past several weeks and died at a hospital in Pune, family sources said.
He passed away at a private hospital here where he was brought in a critical condition last week.
"Padgaonkar was brought to Ruby Hall Clinic here from Prayag Hospital in a critical condition on November 18. When he was brought here, he was on ventilator support and there was multi-organ failure. From the day of admission, he was on dialysis and ventilator support," Sanjay Pathare, Director, medical services, Ruby Hall Clinic said.
Pathare said a team of doctors tried to revive Padgaonkar, but he breathed his last today.
Born in Pune in 1944, Padgaonkar did his schooling from St Vincent's High School and later graduated from Fergusson College in political science.
He began his career in journalism at an early age and joined the Times of India as its Paris correspondent after receiving a doctorate in Humanities in 1968.
He served the paper in various capacities before he was appointed its editor in 1988, a post he held for six years. In between, from 1978 to 1986, he also worked with UNESCO in Bangkok and Paris.
Padgaonkar was appointed as one of the members of the three-member interlocutors group on Jammu and Kashmir, set up by the government after continuous unrest in the Valley in 2008. The veteran journalist had once said that he held the second most important job in the country after the Prime Minister.
Founder editor of the online news website The Wire Sidharth Vardarajan said it was a "terrible loss".
"Just heard that my friend and former editor, Dileep Padgaonkar, passed away in Pune. Terrible loss, feel gutted," he said on Twitter.
Senior journalist Rajdeep Sardesai said Padgaonkar was "a man of culture and intellect".
"My first editor Dileep Padgaonkar, a man of culture and intellect, someone who encouraged young talent, has passed away," he tweeted.
Railways Minister Suresh Prabhu tweeted, "Very saddened by passing away of dear friend, veteran journalist Dileep Padgaonkar. Condolences to the family.