Plans for a £400m energy-from-waste incinerator on the outskirts of Merthyr Tydfil have been withdrawn.
Covanta's Brig Y Cwm application was among four proposals initially short-listed by Prosiect Gwyrdd, a consortium of five councils.
Covanta said the authorities' approach made the project "unviable".
Last month a BBC probe found Covanta has a history of breaking environmental regulations in the United States. The company denied any risk to health.
The five south Wales local authorities are looking for a method of disposing of so-called "residual" or non-recyclable waste.
Four companies were initially in the running for the lucrative 25 year contract, but one, Waste Recycling Ltd, pulled out in April 2011.
Of the two proposals remaining, Veolia ES Aurora Ltd plans an Energy Recovery Facility (ERF) at Bowlease Common, south of the Corus Llanwern Steelworks in Newport.
Viridor Waste Management Ltd is proposing a merchant Energy from Waste (EfW) with combined heat and power facility at Trident Park, Cardiff.
Covanta said its withdrawal had "nothing to do with local opposition".
In a statement, the US-based company said: "We were looking to provide a national solution for much of the waste in Wales which is currently going to landfill.
"This would have provided a low disposal cost, low carbon and highly efficient solution.
"After a long search we wanted to place our multi-million pound inward investment at Merthyr Tydfil which is one of the most depressed towns in Wales.
"It would have been transformed by this level of investment.
"However, the local authorities have adopted a fragmented approach (not a national approach) to dealing with residual waste.
"This makes the plant unviable. We have therefore decided to terminate the planning process and concentrate on our other UK projects."
Merthyr Tydfil MP Dai Havard, who opposed the incinerator plan, said he was delighted Covanta has pulled out.
Huw Lewis, AM for Merthyr Tydfil and Rhymney, said it was a "clear victory for everyone who has campaigned to oppose this huge incinerator development".
"The campaign against the incinerator has united people from all communities in Merthyr Tydfil and Rhymney, people from all backgrounds and of all shades of political opinion.
"I am thoroughly delighted that this application has been withdrawn. Our communities can now breathe a sigh of relief," he said.
Friends of The Earth also welcomed the news.