It has called in extra nursing staff and put surgeons on stand-by to cope with any casualties among the crowds over the weekend.
Braced for an influx of thousands of visitors, bosses have increased capacity in casualty and maternity, and has an extra operating theatre ready.
Elaine Vinter, of York Teaching Hospitals NHS trust, said: "No one has ever experienced this before. It is not extra beds we are providing because we only have a limited capacity.
"But there are extra staff in the fracture clinic in case anyone is injured in the crowds.
"We have not had to cancel leave but people who can easily get to work by walking are coming to work and on-call staff normally available on the phone are staying over in York and have been given accommodation.
"Mothers-to-be expecting this weekend have all been sent a letter giving them lengthy advice, including that they come in a bit early or call for reassurance.
"We cannot predict when babies might get here," she continued, adding she hoped that the excitement of the event would not lead to early unexpected deliveries."
Hospital visitors are also being advised to leave their cars at home on Sunday.
Bosses are warning of major congestion and say visitors should walk, cycle or use public transport.
The hospital has a large on-site car park intended for patients, staff, and visitors.
It is not normally abused by the general public because there is usually plenty of alternative parking.
But car park and security staff will be on duty at all entrances from Friday to Monday to ensure the parking is not being abused.
Jan Aspinall, deputy director of Operations, said: “Although Wigginton Road will not be affected by official road closures it is expected it will be severely congested due to nearby roads being closed.
"We are hoping things will be back to normal by the evening visiting session at 6.30pm.”
Visitors should park in the multi-storey car park except for blue badge holders who will remain unaffected.