The first 2+2 was held in New Delhi September last year.
The first-ever Indo-US ministerial 2+2 dialogue on American soil is expected to be a "highly qualitative and productive" meeting during which some key agreements that will augment the bilateral security ties could be signed, according to senior officials.
External Affairs Minister S Jaishankar along with Defence Minister Rajnath Singh would be hosted by their American counterparts Secretary of State Mike Pompeo and Defense Secretary Mark Esper at the Foggy Bottom headquarters of the State Department on Wednesday.
The first 2+2 was held in New Delhi September last year after the mechanism was approved by Prime Minister Narendra Modi and President Donald Trump.
The 2+2 on December 18 comes after a record four meetings between PM Modi and Mr Trump this year, including the massive joint address by the leaders in Houston in September.
"The 2+2 dialogue is the highest-level institutional mechanism between India and USA that brings together our perspectives on foreign policy, defence and strategic issues. This is the first time such a meeting is taking place in the USA," said the Indian Ambassador here Harsh Vardhan Shringla.
"A lot of progress has been made in the areas of foreign policy and defence between our two countries and we are looking forward to a highly qualitative meeting," Mr Shringla told PTI ahead of the 2+2 meeting.
The fact that the meeting is occurring is a success in itself and testament to the priority both the US and India place on the relationship and cooperating to advance their common interests, said Joe Felter, US Deputy Assistant Secretary of Defense for South and Southeast Asia.
Mr Felter, who played a key role in the first 2+2 last year in the defense side of the talks, is a senior research scholar at Center for International Security and Cooperation and a research fellow at the Hoover Institution both at the Stanford University.
"The ministers will likely reaffirm commitment to building the US-India relationship and importance of working together to achieve a shared vision for the future -- one where India assumes its natural role as a major power and net security provider in the region," Mr Felter told PTI.
It is very well possible that the two countries formally sign the Industrial Security Annex to the General Security of Military Information Agreement (GSOMIA-ISA).
This, he said, is a key enabling agreement along with Communications Compatibility and Security Agreement (COMCASA) signed in the inaugural 2+2 dialogue and will allow greater tech transfer.
There is a high possibility of announcements on pending defence sales like MH-60R helicopters, MK-45 naval guns and other systems under consideration.
"Shared values and interests should factor in to defense and security investments example when you purchase a major weapons system like a fighter jet you are not just getting technology and weapon system but are investing in a long-term relationship with the seller and enhancing interoperability with the seller and other countries using the same platforms," Mr Felter told PTI in response to a question.
While the 2+2 format had a very successful launch last year, this year the relationship faces "strong headwinds", according to Rick Rossow from the CSIS think-tank.
Political issues in both nations, but particularly India, indicate a reduced focus on global affairs.
The differences over trade issues, while on pause, still sits in the backdrop. And India's decision to acquire the Russian-made S400 missile defense system looms as well, he said.
"However, we appear close to finalising some important new agreements that will augment our security relationship. Notable among them are the Industrial Security Annex (ISA) and the Basic Exchange and Cooperation Agreement (BECA)," Rossow told PTI.
The ISA allows India's private sector to handle sensitive defense production, while the BECA agreement opens the door for deeper geospatial intelligence hearing.
The importance of the India-US 2+2 ministerial comes from the fact that the only other country with which India holds such a dialogue is Japan, its close partner and friend in Asia, observed Aparna Pande, director of Hudson Institute''s Initiative on the Future of India and South Asia at the think-tank.
There is the likelihood the two sides will agree on some more arms purchases, she said.
The US has always wanted India to focus more on Indo-Pacific and align itself with American grand strategy.
While both countries agree on the importance of a Free and Open Indo Pacific, India would like equal focus on the western end of the Indo-Pacific -- the Gulf and Middle East and North Africa -- as is given to the East and South China Sea part of Indo Pacific, she added.
China has been flexing its military muscles in the Indo-Pacific region.
Beijing asserts nearly all of the South China Sea as its territory, while Taiwan, the Philippines, Brunei, Malaysia and Vietnam all claim parts.
"There will, however, also be discussions on issues where the two do not see eye to eye, including India's purchase of military equipment from Russia, the trade issue between India and the US, the issue of Iran, and the peace negotiations in Afghanistan," Ms Pande added.
"Further, currently India is facing intense scrutiny in Washington DC over the last few months over Kashmir, the National Register of Citizens and the Citizenship Amendment Act. It is to be expected that these issues will also come up during the conversations especially with the State Department," Ms Pande said.