The Omagh Road, between Ballygawley and Omagh, is closed in both directions near its junction with the Garvaghy Bridge Road following a serious road traffic collision.
The road is likely to remain closed for a number of hours.
Diversions are in place however delays are expected.
A spokesperson for the Northern Ireland Ambulance Service (NIAS) said: “The Northern Ireland Ambulance Service received a 999 call at 10.17pm on Monday following reports of an crash in the Omagh Road area, Garvaghey.
“NIAS dispatched three emergency ambulances, an ambulance officer and a rapid response paramedic to the scene.
“Following assessment and initial treatment at the scene, two people were taken to Craigavon Area Hospital by Ambulance.”