Police were called to the scene at 0253 BST on Monday
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Thousands of motorists were affected when the A55 eastbound was closed for more than six hours after a collision involving a car and a van.
North Wales Police said the incident occurred shortly before 0300 BST near Caerwys, Flintshire, and a woman, 43, was in a "serious condition".
The force said the road re-opened at 0940 BST.
The westbound carriageway was also closed for more than three hours, but was re-opened at 0624.
The closure is likely to have caused rush-hour delays to commuters travelling along the main route in and out of north Wales.
The police spokeswoman said the injured woman, who had been driving a red Rover 211, had to be freed by fire-fighters. She was taken to Ysbyty Glan Clwyd in Bodelwyddan, Denbighshire.
The other vehicle involved was a Citroen panel van.
Any witnesses are asked to call North Wales Police on 0845 6071001 (Welsh) or 0845 6071002 (English).
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