The accident happened around 7.55am today near Aston Tirrold and no arrests have been made.
This morning, a white Ford Transit van, which was travelling towards Blewbury, and a green Honda Civic, which was travelling towards Goring, were involved in a collision.
Both drivers were taken to hospital.
Sadly the driver of the Honda, later died.
His next of kin have been informed and are being supported by specially trained officers.
The driver of the van has since been discharged.
Investigating officer PC Darren Baker, of the Serious Collision Investigation Unit, said: “Sadly a man has died following this incident and we are carrying out an investigation to establish exactly what happened.
“I am appealing to anyone who may have witnessed this incident, or who may have been in the area around this time, to please get in touch.
“I would also ask anyone with dash-cams to check footage in case it may have captured either of the vehicles before the incident.
“Anyone with information can contact police by calling 101 or making a report online, quoting reference 43210189150.”