Part of the A38 was shut for 11 hours, after a crash involving a car and lorry that left a motorist with life-threatening injuries.
The collision happened in Burton-upon-Trent, near the Staffordshire/Derbyshire border, on the A38 southbound slip road towards the A5121 at about 01:35 BST.
An Audi driver in his 20s, who had serious head injuries, was taken to Queen’s Medical Centre in Nottingham.
Two people from the lorry, including one who was conveyed to Royal Derby Hospital, had injuries not believed to be serious, the ambulance service said.
The second person from that vehicle was discharged at the scene.
The southbound route reopened between the A5121 and A50 Derby/Toyota island junctions about 12:40 BST.
The northbound route reopened shortly before 11:00 BST, National Highways said, after being shut overnight.
Congestion was reported earlier on surrounding routes through Hatton, Newton Solney, Willington, Rolleston-on-Dove and Burton-upon-Trent.
Police have asked anyone with information, CCTV or dashcam footage to get in touch with investigators.
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