An inquiry into avoidable deaths at Stafford Hospital will look at why the health care system tolerated a "terrible standard of service".
A 2009 report condemned conditions at the hospital, which are said to have caused hundreds of avoidable deaths.
The last government ordered a private investigation, but refused a wider public inquiry.
But in June the coalition government said the families of those who died deserved to know what went wrong.
It is the fifth inquiry into the higher than expected deaths at Stafford Hospital between 2005 and 2008.
Inquiry chairman Robert Francis QC, who will start hearing expert evidence next week, also chaired the fourth inquiry, which he criticised for its narrow remit.
The inquiries were ordered after the 2009 Healthcare Commission report listed a catalogue of failings including receptionists assessing patients arriving at A&E, a shortage of nurses and senior doctors and pressure on staff to meet targets.
The start of Monday's inquiry was delayed after one of the relatives objected because family members and the media were in a different room from the inquiry chairman and his panel.
In setting out the public inquiry framework Mr Francis said he would not revisit the harrowing cases of deceased patients brought to light in the fourth inquiry, which was held in private.
Instead he said he wanted to look at the structure of the NHS and the actions and inactions of management to see how the failings had come about and why they had remained undetected for so long.
He also paid tribute to the relatives and campaigners from groups such as Cure the NHS, which was set up to highlight problems at Stafford Hospital.
He said everyone was there because of the "terrible standard of service inflicted on so many of the patients who went to Stafford Hospital and their families".
"Last year, in my first inquiry, I sat and listened to many stories of appalling care," he said.
"As I did so, the question that went constantly through my mind was, why did none of the many organisations charged with the supervision and regulation of our hospital detect that something so serious was going on, and why was nothing done about it?"
Tom Kark QC, leading counsel to the inquiry, said the purpose of the inquiry was to focus not on what went wrong but how it was allowed to go on for so long.
He said: "Why did no-one act to correct the serious errors that were undoubtedly taking place?
"Why did the health care system as a whole tolerate what were clearly unacceptable standards of care?
"Why did those who should have been in the right position to take steps not do so? "
Julie Bailey, who set up Cure the NHS, said: "This will get to the truth. We really believe this will be a full examination of what went wrong, not just at the hospital but with the regulatory bodies.
"We believe that if they had done something about it when we first reported concerns, it would have saved many, many lives within this community," she said.
Problems at Stafford Hospital, run by the Mid Staffordshire NHS Trust, were first exposed by an NHS regulator in March 2009.
The Labour government then started several investigations.
These included an independent inquiry led by Mr Francis, but it was held in private and did not have the power to compel witnesses to give evidence.
When it reported in February it said the trust had been driven by targets and cost-cutting.
But campaigners said the failings went far wider than the hospital itself, and the broader NHS and regulators should have realised there were problems and stepped in.
They demanded a full public inquiry with stronger legal powers.
In June, Health Secretary Andrew Lansley announced Mr Francis would continue the work he had already done on investigating the hospital by leading an inquiry.
The inquiry will consider more than a million pages of evidence and will hear from dozens of witnesses.
Stafford Hospital management have said they have been working hard to improve patient care over the past 18 months.
The new chief executive, Anthony Sumara, said they had taken on 140 more nurses, improved training, and changed procedures in the areas which had problems.
The Mid Staffordshire NHS Foundation Trust Public Inquiry is being held at the offices of Stafford Borough Council.