In jurisprudence, prosecutorial misconduct is a procedural defense; via which, a defendant may argue that they should not be held criminally liable for actions which broke the law, because the prosecution acted in an "inappropriate" or "unfair" manner. Such arguments may involve allegations that the prosecution withheld evidence or knowingly permitted false testimony. This is similar to selective prosecution. In late 1993, the 6th US Circuit Court of Appeals ruled that John Demjanjuk had been a victim of prosecutorial misconduct during a 1986 trial in which federal prosecutors withheld evidence. Demjanjuk's sentence was overturned, but he lost when his case was retried.

In the 1995 murder trial of O. J. Simpson, the defense argued that Los Angeles Police Department detective Mark Fuhrman had planted "evidence" at the crime scene. Although Fuhrman denied the allegations, Simpson was found "not guilty". In USA Today (August 24, 1995), Francis Fukuyama stated, "[Such defenses lead to] a distrust of government and the belief that public authorities are in a vast conspiracy to violate the rights of individuals."

Despite such, the defense has been successful roughly 1 out of 6 times it has been used from 1970 to 2003. During that period, judges have cited misconduct by prosecutors as a reason to dismiss charges, reverse convictions, or reduce sentences in 2,012 cases, according to a study by the Center for Public Integrity released in 2003; the researchers looked at 11,452 cases in which misconduct was alleged.

A debate persists over the meaning of the term. Prosecutors have asked judges to stop using the term to refer to an unintentional error, and to restrict its use to describe a breach of professional ethics. E. Norman Veasey, the chief justice of Delaware Supreme Court, answered one such request in 2003 by noting the term's extensive use in rulings over the past 60 years. "We believe it would be confusing to change the terminology in view of this history," he wrote in reply.