The man's car left the southbound section of the motorway near Stirling and he was flown by air ambulance to the Southern General Hospital in Glasgow.
It was shut in both directions last night for around three miles between junction 10, Craigforth Rounabout to junction 11 at Keir Roundabout on the outskirts of Dunblane.
At one point the delays stretched for three miles.
The man was driving southbound when the crash happened just before 3pm.
A Central Scotland Police spokesman said: "We can confirm there has been a one vehicle road traffic collision on the south-bound carriageway of the M9.
"One male was in the vehicle, and he has been airlifted to the Southern General."
Police were trying to contact relatives of the man, who has not been named.
The northbound carriageway was closed to allow the air ambulance to land and take-off, but later reopened.
A police spokesman added: "There is no indication as yet what caused the accident. A full investigation will be carried out.
"The man's next of kin are being identified and will be informed."
The main route remained open to north-bound traffic.