Letten stepped down as the investigation of misconduct by two of his two top prosecutors continues.
CLICK HERE to listen to Letten's resignation speech....
At a news conference at his downtown office, Letten said that he would stay on for a short period "to assist the transition" to a new chief prosecutor.
The Department of Justice released a statement saying Dana J. Boente had been appointed as interim U.S. Attorney for the Eastern District of Louisiana.
Two prosecutors who served as supervisors under Letten are targets of the investigation.
One is Sal Perricone. He resigned in March after acknowledging he criticized judges and politicians and commented on cases in anonymous posts on a local newspaper's website.
Then Letten demoted his top assistant, Jan Mann, last month after she admitted posting several anonymous comments on the same site.
Letten rose to fame by winning the racketeering conviction of former Louisiana Gov. Edwin Edwards. He has served as U.S. attorney for the Eastern District of Louisiana since 2001.