The outgoing chief prosecutor at the International War Crimes Tribunal in The Hague says she is disappointed that some fugitives are still at large.
Ms del Ponte gained a reputation for the ruthless pursuit of fugitives
The fact that Ratko Mladic and Radovan Karadzic had not been arrested was a "stain" on the tribunal's "great achievements", she said.
Ms del Ponte was speaking in The Hague at her final press conference as head of the tribunal.
She is due to be replaced next year by Belgian prosecutor Serge Brammertz.
He is heading the investigation into the 2005 killing of former Lebanese Prime Minister Rafik Hariri.
"The fact that Ratko Mladic and Radovan Karadzic are still at large is a stain on our work - a stain on all these great achievements. And as you know, I am very disappointed by this," she told reporters.
Ms del Ponte also repeated her plea that the tribunal - set up to try war crimes from the former Yugoslavia - should stay open until its four final fugitives were caught.
It is due to close in 2010.
Ms del Ponte also called for shorter trials and an end to cross-examination of witnesses by the defence, saying they should not be victimised again.
She also condemned the practice of allowing prisoners on trial to go home for the Christmas holidays, from which 12 defendants had benefited this year.
During her eight years as the world's most powerful criminal lawyer, Carla Del Ponte has helped to bring many war crimes suspects to court and has become a champion to victims seeking justice.
She is to become the Swiss ambassador to Argentina in the new year.
Between them, Radovan Karadzic and Ratko Mladic face 16 counts of genocide, crimes against humanity and violation of the laws of war in Bosnia-Herzegovina between April 1992 and July 1995.
They were charged and indicted by the UN war crimes tribunal at The Hague in 2005, but remain at large.
Also at large are Stojan Zupljanin and Goran Hadzic.