Asked by the presiding judge at the court in the northern city of Oldenburg whether the charges against him were accurate, Niels Högel replied "yes".
"What I have admitted took place," the 41-year-old added.
A moment of silence
Immediately before the trial, Judge Sebastian Bührmann asked all those present to stand up for a minute of silence. "All their relatives deserve to be honoured," said Bührmann, adding that this is independent of whether Högel had anything to do with their death or not.
"We will make every effort to seek the truth," Bührmann promised.
Addressing Högel, he said: "I will negotiate fairly with you, I will negotiate openly with you in good things, and in bad."
A public prosecutor had dealt with each of the 100 cases. Högel had already been sentenced to the maximum sentence of life imprisonment in 2015 for the death of six patients in the Delmenhorst Intensive Care Unit.
According to the public prosecutor, Högel injected his victims with a drug that had deadly side effects. He then tried to revive the patients - which in many cases failed. His motive was said to be boredom and a craving for recognition in front of colleagues.
The trial is complex and costly. The public prosecutor's office has named 23 witnesses and 11 toxicological and forensic experts.
"We fought for four years for this trial and expect Högel to be convicted of another 100 murders," said Christian Marbach, the spokesman for the relatives, whose grandfather was killed by Högel. "The goal is for Högel to remain in prison as long as possible."
Not all of the more than 120 joint plaintiffs appeared on Tuesday. In the reserved rows of seats, many chairs remained empty.
'Little, vulnerable mass murderer'
Prosecutors say at least 36 patients were killed at a hospital in Oldenburg where he worked, and about 64 more at a clinic in nearby Delmenhorst, between
2000 and 2005.
More than 130 bodies of patients who died on Högel's watch have been exhumed, in a case investigators have called "unprecedented in Germany to our knowledge".
One of the more than 100 co-plaintiffs in the trial, Christian Marbach, said it was a scandal that Hoegel had been allowed to kill with impunity for such an extended period of time without hospital authorities or law enforcement intervening.
"They had everything they needed (to stop him) -- you don't have to be Sherlock Holmes," Marbach, the grandson of one of the patients, told AFP.
He later expressed surprise about Högel's quick confession, which was broadcast on two large screens to the courtroom audience.
"I didn't expect it to happen today," he said.
"We now have a chance to make some real progress."
Marbach said the defendant seemed remarkably composed as he admitted to the
extraordinary list of killings.
"He looks like a little, vulnerable mass murderer."
Caught in 2005 while injecting an unprescribed medication into a patient in Delmenhorst, Högel was sentenced in 2008 to seven years in prison for attempted murder.
A second trial followed in 2014-15 under pressure from alleged victims' families, who accused prosecutors of dragging their feet.
He was found guilty of murder and attempted murder of five other victims and given the maximum sentence of 15 years.
It was then that Högel confessed to his psychiatrist at least 30 more murders committed in Delmenhorst. That prompted investigators to take a closer look at suspicious deaths in Oldenburg.
After he took the stand Tuesday, Högel said that he began taking painkillers shortly after becoming a nurse in 1999 as he felt overwhelmed by the job in the intensive care unit.
"It was the stress -- I found (the work) easier on medication," he said. "I should have quit."
Investigators say the final toll could top 200 but fear they might never know for sure because the bodies of many possible victims were cremated.
Högel appears to have followed a similar procedure each time, first injecting a medication that triggered cardiac arrest, followed by an often futile attempt at resuscitation.
Prosecutors say he was motivated by vanity, to show off his skills at saving human lives, and by simple "boredom".
The choice of victim appears to have been entirely random, with their ages ranging from 34 to 96.