Patriciu Achimas-Cadariu stepped down as authorities began an investigation into how a sub-standard disinfectant was used in some 50 hospitals.
According to media reports, the disinfectants were greatly diluted, making them ineffective, and were also overpriced.
An inspection by health officials last week found the poor quality disinfectants in 50 hospitals, including the nine biggest ones in Bucharest.
It is believed to have led to the high number of infections, often fatal, contracted by patients in the hospitals, a situation that has generally not shown up in official statistics, analysts said.
This latest scandal comes just three months after several dozen babies were hospitalised, and three of them died, suffering from an infection the cause of which has never been determined.
On Friday Romanian President Klaus Iohannis called for an “urgent plan of action” to deal with the health crisis.
Prosecutors have opened an inquiry and on Saturday the headquarters of the company allegedly linked to the scandal, Hexi Pharma, and also the home of its boss. were searched.