Harsh Vardhan's resignation comes as the centre battles criticism of handling of the second Covid wave.
Health Minister Harsh Vardhan and his deputy Ashwini Chaube both resigned today ahead of Prime Minister Narendra Modi's cabinet reshuffle, becoming the most significant casualties of a mega government reset seen by many as course-correction before key polls. They are among the dozen ministers asked to go. Law Minister Ravi Shankar Prasad and Environment Minister Prakash Javadekar have also resigned.
Other Union Ministers to quit are: Thaawarchand Gehlot, Ramesh Pokhriyal Nishank, Santosh Kumar Gangwar, Babul Supriyo, Dhotre Sanjay Shamrao, Rattan Lal Kataria, Pratap Chandra Sarangi and Debasree Chaudhuri.
Their resignations comes as the government battles criticism of its handling of the second wave of Covid in April-May, which ambushed India's health infrastructure and left tens of thousands desperate for oxygen, hospital beds and vaccine. Images of bodies floating in the Ganga or washing up on its banks in Uttar Pradesh and Bihar played out in India and abroad.
With cases on the wane, the government's next priority is to stave off a third wave of the virus. This hinges on the government's vaccination plan, which, under the Health Ministry, is also seen to be floundering with the pace not picking up and supply of doses remaining a concern.
The Health Ministry resignations are a big risk when the move could be seized by the opposition as a sort of political victory and vindication after their daily attacks on the government's Covid handling. But sources said Prime Minister Narendra Modi wanted to send out a strong message that performance was key.
Senior Congress leader P Chidambaram was among the first to comment on the development.
"The resignations of the Union Health Minister and the MoS Health is a candid confession that the Modi government has utterly failed in managing the pandemic," Mr Chidambaram tweeted.
Harsh Vardhan, a doctor, enjoyed a sterling record in his past stints as health minister, both at the Centre and in Delhi before that. But the scale of devastation in the second surge was an unprecedented challenge.
Education Minister Ramesh Pokhriyal Nishank and Labour Minister Santosh Gangwar were also assessed poorly in the government's tackling of the pandemic.
Mr Gangwar paid for his ministry's abysmal handling of the migrants and jobs crisis in the early months of the pandemic, when the country was in lockdown, according to Labour Ministry sources.
The Supreme Court recently indicted it for its failure to set up a portal for registering unorganised and migrant workers. "The lackadaisical attitude of the Ministry of Labour is unpardonable," the Supreme Court had said on June 29.
In the weeks leading to the revamp, PM Modi and top leaders like Union Home Minister Amit Shah and BJP chief JP Nadda carried out a detailed review of performances, especially of those who had a role in the Covid fight.
Forty-three ministers are being sworn in today as part of the cabinet reshuffle, the first in PM Modi's second term.