Pointing to the historic nature of the trip, a senior US official said: "It's a pretty big deal for the Laotians, and we will underscore a number of areas that we're working on together."
These include left over ordnance from the war as well as the continuing effects of the defoliant Agent Orange, used by US forces to try to flush out the Vietnamese communist forces.
But one of the main thrusts of the trip will be talks on controversial plans by Laos to build a massive dam on the Mekong River, which governments and environmentalists warn could have a devastating effect on millions of people.
Clinton, who will arrive from a brief visit to Hanoi, will be only the second secretary of state to visit Laos after John Foster Dulles, who spent a day in the then-monarchy in 1955.
She was invited to Laos by Foreign Minister Thongloun Sisoulith in 2010 who was the first top Laotian official to visit Washington since the Soviet-backed communist rebels swept to power, ousting the monarchy, in 1975.
"One of the reasons that we're going to Laos is to try to get greater clarity on what the status of a number of different water projects are in Laos, Cambodia, and Vietnam," the US official added, asking to remain anonymous.
The $3.8 billion hydroelectric project at Xayaburi, led by Thai group CH Karnchang, has sharply divided the four Mekong nations -- Laos, Vietnam, Cambodia and Thailand -- who rely on the river system for fish and irrigation.
State media said last week Laos has pledged to stall the construction of the dam until its neighbours' environmental concerns have been answered.
Deputy Minister of Energy and Mines Viraphonh Viravong told state-run Vientiane Times changes to the project will address two major issues -- fish migration and sediment flow -- by including a passage to allow 85 percent of fish to travel along the river and a "flushing system" to prevent build up.
The mooted 1,260 megawatt dam, the first of 11 on the key waterway, has become a symbol of the potential risks of hydropower projects in the region and the Mekong nations have tussled over its varying impact.
Activists say the dam projects could spell disaster for 60 million people who depend on the Mekong waterway -- the world's largest inland fishery.