His motive, they say, was to impress colleagues by trying to resuscitate the very patients he had attacked.
Hoegel is already serving a life term for killing people in his care.
The latest trial, which is expected to last until May, follows toxicology tests on the exhumed remains of others.
Hoegel is now said to have killed 36 patients in Oldenburg and 64 in nearby Delmenhorst between 1999 and 2005.
The BBC’s Jenny Hill in Berlin says the case is sensitive for German health authorities which are accused by relatives of turning a blind eye to Hoegel’s murderous activity.
If found guilty of all the deaths, he would become one of Germany’s worst post-war serial killers.
Investigators say he may have killed even more but potential victims have been cremated.
“I hope he will be found guilty on each count so that the loved ones can finally find some closure,” said Petra Klein, who runs a victims’ support group.
Relatives of his alleged victims are expected to pack the court.
Hoegel was first caught in 2005 injecting unprescribed medication into a patient in Delmenhorst. In 2008 he was jailed for seven years for attempted murder.
In 2014-15, a second trial found him guilty of two murders and two attempted murders and he was given the maximum sentence.
He said he was “honestly sorry” and hoped families would find peace. He said the decisions to carry out his crimes had been “relatively spontaneous”.
However, during the trial he confessed to a psychiatrist that he had killed up to 30 people.
Investigators then widened the investigation, exhuming 130 former patients and looking for evidence of medication that could have triggered cardiac arrest. They also pored over records in the hospitals he worked at.
Records at the Oldenburg hospital showed rates of deaths and resuscitations had risen when Hoegel was on shift, German media reported.