The incident took place on the N24 in Ballynoran this morning at about 7.25am.
The collision involved a van and a lorry, with the van driver, a man in his 40s, fatally injured and pronounced dead at the scene.
A man in his 60s who was driving the lorry was taken to Waterford University Hospital for treatment of serious injuries.
The road remains closed with local diversions in place as the scene is being examined by Forensic Collision Investigators.
Gardaí are appealing to anyone who may have witnessed the collision, or who may have any information in relation to the collision, to come forward.
Road users who were travelling on the N24 between Kilsheelan and Carrick-On-Suir between 7.20am and 7.30am this morning have also been asked to contact Gardaí.
Anyone with any information can contact Clonmel Garda Station on 052 6177640, the Garda Confidential Line on 1800 666 111 or any Garda station.
