Wales' health boards would be scrapped and major hospitals placed under one body, in new Plaid Cymru plans.
The proposals are expected to be central to the party's campaign to win power in the 2016 assembly election.
Local councils would take charge of community services, such as GPs' surgeries, district nurses and mental health, under the plans.
Welsh ministers said it would "break up the NHS" with "years of chaotic, confusing and costly reorganisation".
Plaid Cymru said delays to treatment would be reduced by integrating much of the health and social care system.
Plaid's health spokeswoman Elin Jones will give details in a speech in Cardiff on Thursday of what she is calling the "biggest change to the way care is delivered since the advent of the NHS in 1948".
She added: "Navigating the complexities of the health and social care system in its current form is confusing and time-consuming for patients, many of whom are in a vulnerable state.
"Anyone who has waited for their social care package to be implemented, or who has a family member who has needed to move from health to social care services, will know that there are often long delays whilst they wait for bureaucratic decisions to take place."
Ms Jones is also expected to set out plans to address what she called the "fundamental unfairness" of the cost of social care.
"If you are diagnosed with cancer then you are likely to be treated for free by the NHS; if you get a diagnosis of dementia your care needs will be met by social care and you will be means tested and possibly charged," she said.
The last re-organisation of the Welsh NHS was in 2009 when 22 local health boards and seven trusts were replaced by the seven current health boards.
Under Plaid's proposals, which the party said could take three years to bring in, responsibility for planning and running acute and specialist hospitals would be carried out by one national hospital board.
Local authorities would manage community services, but the party said some larger authorities could devolve responsibility to large groups of GPs.
An estimate of the costs of some of the changes will be released on Thursday, with full budget proposals announced closer to the election.
The plans were ridiculed by the Welsh Labour government as "the end of the NHS as we know it",
A spokesman for Health Minister Mark Drakeford said: "Plaid is proposing little more than the break up of the NHS and condemning the health service to years of chaotic, confusing and a hugely costly reorganisation with these nonsensical plans to give local politicians direct control of planning community services, including GP care and mental healthcare, at a time when money should be invested in frontline services."
Conservative shadow health spokesman Darren Millar said "another expensive change" was not the answer to the "significant problems" facing the Welsh NHS.
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