Investigators said two men came into the bank just before 9:30 a.m. Monday. One of them fired a gun into the ceiling twice.
The alleged robbers got away with an undisclosed amount of cash.
There were employees and customers in the bank when it happened. Nobody was hurt.
Police said they suspect the men could be the same ones who held up the same bank back in June.
Anyone with information is asked to call Sanford police at (919) 775-8268.