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In December 2000, Durham revealed secret FBI documents that convinced a judge to vacate the 1968 murder convictions of Enrico Tameleo, Joseph Salvati, Peter J. Limone and Louis Greco because they had been framed by the agency. In 2007, the documents helped Salvati, Limone, and the families of the two other men who had died in prison win a US$101.7 million civil judgment against the government.

In 2002, Durham helped secure the conviction of retired FBI agent John J. Connolly Jr., who was sentenced to 10 years in prison on federal racketeering charges for protecting Bulger and Flemmi from prosecution and warning Bulger to flee just before the gangster’s 1995 indictment.

Durham’s task force also gathered evidence against retired FBI agent H. Paul Rico who was indicted in Oklahoma on state charges that he helped Bulger and Flemmi kill a Tulsa businessman in 1981. Rico died in 2004 before the case went to trial.

Durham also led a series of high-profile prosecutions in Connecticut against the New England Mafia and corrupt politicians, including former governor John G. Rowland.

In 2008, John Durham was appointed by then-Attorney General Michael Mukasey to investigate the destruction of CIA videotapes of detainee interrogations. On November 8, 2010, Durham closed the investigation without recommending any criminal charges be filed. Durham’s final report remains secret but was the subject of an unsuccessful lawsuit under the Freedom of Information Act filed by The New York Times reporter Charlie Savage.

In 2009, Attorney General Eric Holder appointed Durham to lead the Justice Department’s investigation of the legality of CIA’s use of so-called “enhanced interrogation techniques”.