As punishment beatings reach record levels in the province, the veteran negotiator, who earned universal respect for his role in breaking the deadlock, made a rare public plea for all sides to keep the deal alive.
His renewed concerns over the health of the agreement are bound to register with President Bill Clinton, who told the Prime Minister, Tony Blair, after King Hussein's funeral that he wanted the Good Friday settlement to stay on track.
Mr Mitchell made his comments during a speech at Liverpool University, where he was given an honorary law degree.
He said decommissioning of weapons was still the main stumbling block but he remained hopeful. "I think it is a very difficult ... issue but the political leaders must not let this chance of peace slip away."
Earlier, Mr Mitchell delivered the university's Institute of Irish Studies annual peace lecture in which he spoke about his four-year role as chairman of the talks aimed at healing divides in Ulster.
He spoke of his admiration for the bravery of politicians in this decade.
"Despite much difference and over many setbacks the governments persevered and for that they deserve more credit than they have got," he said.
"Tony Blair and Bertie Ahern were brilliant in bringing the process to a conclusion but they would be the first to acknowledge that their predecessors set the stage and made that conclusion possible. To those predecessors I say: 'Well done'."
But he also spoke of what he described as "the especially black and dangerous time" of Christmas 1997 and early 1998 when there was "a definite effort by men of violence on both sides to destroy the process". He identified the murder of Billy Wright in prison as a particularly difficult time as it led to a "sharp increase in sectarian killings".
Mr Mitchell said the turning point came when he decided to set a deadline for the talks. "I was conscious that the absence of a deadline guaranteed failure although I accepted that the existence of a deadline could not guarantee peace, but made it possible."Reuse content