A 45-year-old man from Maesteg died in a collision on the A465 at Resolven near Neath, police say.
A white Renault articulated lorry vehicle crossed the central reservation and collided with a white Citroen van travelling on the opposite carriageway at around 3.40pm on Thursday.
The driver of the van was pronounced dead at the scene, while the van's passenger and lorry driver were taken to Morriston Hospital for treatment.
South Wales Police are appealing for anyone who witnessed the collision to contact them.
More top news
Three South Wales police officers face allegations of misconduct regarding paedophile and former Lost Prophets singer Ian Watkins
A football-loving Welsh couple set off to see the Euros in Lille - but ended up in the wrong Lille more than a hundred miles away.
While Belgium fans will heavily outnumber their Welsh counterparts in Lille, Wales know that they are unbeaten in the last three meetings.