New security guards will be put in charge of making sure Bernie Madoff does not escape from his penthouse.
Queens prosecutors, MTA officials and a former judge all accused Casale of lying in a previous investigation.
In Casale's resignation letter, he said his security firm does not have the global resources to monitor Madoff's worldwide properties.
The new security firm set to take over is run by former leading FBI agent Ed Stroz.
Madoff remains under house arrest as investigators continue to probe his alleged $50 billion Ponzi scheme.