It is not the first time a sheet of glass has crashed from the empty building. In 2006, a window fell on to a vehicle.
The building has been the target of vandalism and squatters, having been unoccupied for more than 10 years.
Dunedin man Guy Pringle said he saw glass on the footpath and on a vehicle parked in Water St about 11pm on Tuesday after a window fell from the top floor of the building.
"Fortunately, there were no pedestrians underneath at the time, although the glass was sent flying in all directions, causing damage to a car below."
Senior Sergeant Mel Aitken, of Dunedin, said police investigated a possible break-in at the building, where it was believed someone was either throwing items or had pushed a window out.
South Canterbury Finance chief executive Lachie McLeod said he would get the building's property manager to ensure it was secure.
The company took possession of the building in December last year to recoup costs after the McEwan Group's plans to turn the building into a Hilton Hotel failed.
Mr McLeod said "good progress" was being made after the building was put up for mortgagee tender.
He declined to comment further.