One of the longest-serving prosecutors in the Sept. 11, 2001, case is stepping down, citing the pressure of his repeated trips to Guantánamo Bay on him and his family.

The prosecutor, Edward R. Ryan, is a Justice Department lawyer who served on a team of civilian and military prosecutors who for 15 years have sought to start the trial of Khalid Shaikh Mohammed and four other prisoners accused of conspiring in the hijackings that killed nearly 3,000 people in New York, in Pennsylvania and at the Pentagon.

Mr. Ryan’s decision was seen as a sign that the case would not be going to trial anytime soon.

He represented the government at the prisoners’ original court appearance at Guantánamo in 2008 and participated in nearly all the pretrial hearings since then.

On Wednesday, Mr. Ryan told family members of victims of the attacks by email that he was leaving “with the heaviest heart” to return to North Carolina, where he was a federal prosecutor before his Guantánamo assignment.

“The challenges that come with the passage of time and trying to work so far from home have simply become too difficult for me and my extended family,” he said.

The case has been mired in pretrial hearings over what evidence would be admissible at the national security trial, which is expected to last more than a year when it eventually starts.

The defendants were held from 2003 to 2006 in the C.I.A.’s secret overseas prison network, known as black sites, complicating efforts to move past the pretrial litigation phase. A key issue is whether the accused voluntarily confessed at Guantánamo after years in which they were deprived of sleep, kept in solitary confinement and interrogated with violence, including waterboarding.

For more than a decade, Mr. Ryan, 62, had close interactions with the Sept. 11 families, both at Guantánamo hearings and in private meetings prosecutors periodically held in Massachusetts, New York and Florida.

“All that knowledge, I’m sad to see him go,” said Kathleen Vigiano, whose husband, Joseph Vigiano, a New York police detective, and brother-in-law, John Vigiano Jr., a New York firefighter, were both killed at the World Trade Center.

At Guantánamo, Mr. Ryan would silently slip into the back row of news conferences inside a dilapidated hangar at the war court compound, Camp Justice, wiping away tears as family members spoke of loved ones killed in the attack and frustration over the long wait for a trial.

His was a commuter job to a commuter courtroom. When not at Guantánamo or at home in North Carolina, he worked out of the headquarters of the chief prosecutor for military commissions in Virginia, not far from the Pentagon.

Mr. Ryan frequently argued in court that the defendants willingly bragged about their roles in the attacks long after their C.I.A. detention had ended.

When defense lawyers found out that some F.B.I. agents had become secret operatives in the black site program, Mr. Ryan defended the arrangement as part of an all-of-government response to the worst attack on U.S. soil in American history.

Mr. Ryan’s argument of voluntary self-incrimination failed in Guantánamo’s other capital case, over the bombing of the Navy destroyer Cole off Yemen on Oct. 12, 2000. A judge threw out the defendant’s confession, ruling that his will to resist had been “intentionally and literally beaten out of him years before” by U.S. government agents. Prosecutors are appealing.

Pretrial hearings in the Sept. 11 case will continue next week without Mr. Ryan. He said in his email to the families that he was honored to represent them and the U.S. government despite “the great sorrow and frustration that we on the team, and all of you have felt at the terrible delays that have plagued us.”

Now only two of the original eight prosecutors are still on the case: Clayton G. Trivett Jr., who started prosecuting cases at Guantánamo as a Navy lawyer, and Jeffrey D. Groharing, who started as a Marine lawyer. Both now serve as civilians.

“We on the prosecution team,” Mr. Ryan wrote, “have done all that our devotion to duty would allow to bring the case to proper resolution. I have great faith that the team will continue the fight, and bring justice to you and our nation.”