The research will focus on the long term medical effects
Anne Sassaman, of the US National Institute of Environmental Health Sciences, and Nguyen Ngoc Sinh, head of Vietnam's National Environmental Agency, signed an agreement laying out specific priorities for future research.
"This framework for collaboration is an important step forward, but the real difficulties lie ahead - agreeing to do the research is the easy part. " Dr Sassaman said in a statement.
"The more difficult task will be to develop research studies that are definitive and address the underlying causes of disease in Vietnam," she added.
Contaminated areas
Key areas for research include spontaneous abortions, miscarriages, congenital malformations, neurological disorders and cancers.
In a pilot project scientists from the American Environmental Protection Agency (EPA) are helping their Vietnamese counterparts to study the impact of Agent Orange at a contamination hotspot near the country's third largest city of Danang.
Priority will also be given to identifying and cleaning up "hotspots," where high concentrations of dioxin still exist.
Call for help
US forces sprayed millions of gallons of Agent Orange on Vietnam during the war that ended in 1975, to deny communist soldiers jungle cover.
The US stopped spraying in 1971 after it was discovered that it contained the most dangerous form of dioxin, TCDD, and caused cancer in rats.
On Wednesday, Vietnam's Red Cross appealed for urgent help for victims of Agent Orange - the poisonous chemical dioxin used during the Vietnam War.
"People affected by Agent Orange need help now and cannot wait years for more research, said the head of Vietnam's Red Cross," said Professor Nguyen Trong Nhan.