The A470 was closed for a number of hours after a man reportedly jumped from a moving vehicle.
The man is now in hospital in a critical condition after what had initially been described as a "multi-vehicle crash" by traffic monitors.
The crash happened near Taffs Well, just to the north of Cardiff.
The incident happened on the southbound side of the road at around 4pm and there were large numbers of emergency services at the scene. A man has been taken to the University Hospital of Wales.
The southbound carriageway reopened at around 7.20pm. The northbound side was also closed from Coryton to Taffs Well in order for a helicopter to land but that carriageway was then reopened.
South Wales Police is appealing for witnesses to two incidents which led to the closure of the A470 Taffs Well earlier today.