The Royal College of Nursing (RCN) is to start balloting members on industrial and strike action over staffing and pay in Northern Ireland.
Voting papers are being posted to RCN members working in health and social care services, with the ballot due to last for four weeks.
The RCN's Northern Ireland director Pat Cullen said there was a pay crisis.
But the Department of Health said the RCN was "making demands it knows the department cannot meet".
It is the first time in the nursing union's 103-year-history that its members have been balloted.
Staff will be asked if they are willing to take industrial action, including strike action, over what Pat Cullen said were the "unacceptable conditions" being faced in healthcare in Northern Ireland.
"Nurses are being expected to work with nearly 3,000 unfilled nursing posts across the system while their pay has fallen far behind colleagues in England, Scotland and Wales," she said.
"Nurses can go anywhere to work and we fear that unless this situation is resolved quickly it will only get worse as our newly-qualified nurses choose to practise elsewhere in the UK and beyond."
Ms Cullen said RCN members had said "enough is enough" and that they had been "left with no choice".
"No nurse wants to take industrial action or strike action but low staffing levels pose unacceptable risks to patients, nursing staff, and the people of Northern Ireland," she added.
The ballot will close on 6 November.
The college said it was asking the public to give their support by signing a petition to demand safe staffing and pay equality for nurses.
The RCN's chief executive Dame Donna Kinnair said the nurses had seen a decade of "great unfairness" and the "grave consequences for their patients".
"Their service has been undervalued and this continues as pay awards fall further behind other countries of the UK," she added.
"Starving a country of enough nurses is a major risk to patient safety, which the nurses of Northern Ireland will not stand by and let happen to their much-loved health service.
"Many months of negotiations failed to achieve a breakthrough and we take these measures to show the strength of feeling in the public and the nursing workforce."
In a statement, a Department of Health spokesperson added: "We do not have the authority to overturn ministerial decisions on localised Northern Ireland pay rates.
"Nor can we make cuts to services to fund the pay increase being sought."