It has divided public sentiment.
The billboard on Hastings River Drive which says "Vaccines &Fluoride Hold Risks" is a political advertisement for the Involuntary Medication Objectors (Vaccination/Fluoride) Party.
The party is competing for a senate seat in the upcoming federal election in May.
Lead candidate Michael O'Neill said they are a "single issue party on any compulsory medication, such as fluoridation or vaccination."
"I have major problems with the current vaccination schedule for children as it stands," Mr O'Neill said.
"I believe it is over-medication.
"It is way too much for young children and their young bodies to deal with."
For Mr O'Neill the issue is personal.
"My oldest son had a very bad reaction to his first vaccine, his second vaccine was even worse.
"Our next child, who is now 32, had zero vaccines and has had impeccable health throughout her life."
Mr O'Neill said Port Macquarie was chosen for the billboard because of the high profile debate over fluoride in the town.
But, not everyone is happy the billboard is on a main thoroughfare in Port Macquarie.
A post by Facebook user Leah Maree criticising the sign on the Port Macquarie Thumbs Up, Thumbs Down page attracted 616 comments.
Port Macquarie mum of one Claire said the billboard was "irresponsible".
There is definitely not much evidence to support their claims and they can definitely pray on the weak minded and the gullible which puts new born babies at risk.Claire
"There was two cases in Sydney of babies too young to be vaccinated for measles catching measles, why should those families been punished?"
Retiree Michael Horton said the billboard was "confrontational" and "he couldn't believe anyone running for parliament on that platform could get elected".
The debate over the billboard comes as NSW is on track for its worst measles outbreak in five years after two young travellers from the state's North Coast became the latest to fall victim to the highly contagious disease.
Last week the Mid North Coast Local Health District urged all pregnant women and parents to be aware of the symptoms of whooping cough and ensure children are vaccinated in time, after a spike in cases.
Acting Director of Public Health for the North Coast Greg Bell said people "would make their own decisions about vaccinations regardless of the billboard" but stressed vaccinations were imperative to public health.
"From a public health view we should do everything to protect the community particularly the most vulnerable, babies are the ones we really want to protect".
"Vaccination is a wonderful way of protecting our little ones, allowing everyone to have a good standard of living."
Mr Bell said vaccination rates on the Mid-North Coast remain strong.
Ninety-two per cent of children by 12 months are vaccinated, a rate that drops to just over 90 per cent by two years.
Claude Outdoor which owns the billboard on Hastings River Drive was contacted for comment.