The collapse of Kabul Bank in 2010 exposed massive high-level corruption, with international donors outraged that aid money was disappearing into private pockets while Afghanistan remained wracked by poverty and violence.
The fraud saw fake companies given loans by the bank, and the cash spirited abroad -- sometimes in airline food trays -- in a sophisticated operation to buy homes in Britain, Dubai, Switzerland and the US.
The scandal touched a brother of former president Hamid Karzai and a brother of late vice president Mohammad Qasim Fahim, both shareholders in the bank, but the police have never investigated allegations against them.
"As our first step in realising our promise to fight fraudulent practices, the Kabul Bank case will be re-opened today in a fundamental way, and will be pursued to ensure people's rights," Ghani said, on only his second day in office.
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"The time for action has come, and as we had pledged, the fight against corruption will be done in a thorough and systematic way."
On the campaign trail, Ghani repeatedly vowed he would pursue those behind what the government previously described as the country's "largest and most complex financial crime".
Ghani, who won a reputation as an anti-corruption campaigner while finance minister from 2002-2004, has hit the ground running after being inaugurated on Monday.
On Tuesday, his government signed a long-delayed bilateral security agreement to allow about 10,000 US troops to stay in the country next year.