The US has activated a land-based missile defence station in Romania, which will form part of a larger and controversial European shield.
Senior US and Nato officials attended the ceremony in Deveselu, southern Romania.
The US says the Aegis system is a shield to protect Nato countries from short and medium-range missiles, particularly from the Middle East.
But Russia sees it as a security threat - a claim denied by Nato.
Relations between the West and Russia have deteriorated since Moscow's annexation of Ukraine's southern Crimea peninsula in 2014.
Nato Secretary General Jens Stoltenberg and other senior officials from the military alliance attended the opening ceremony at an old Romanian air base in Deveselu., 180km (110 miles) south-west of Bucharest.
The site hosts radar and SM-3 missile interceptors, and will be integrated into Nato's missile shield when the bloc meets this summer.
Both Nato and US officials have attempted to reassure Russia that the shield in Romania, and a similar one in Poland, does not undermine Russia's strategic nuclear deterrent.
"The interceptors are too few and located too far south or too close to Russia to be able to intercept Russian intercontinental ballistic missiles," Mr Stoltenberg said.
He said the interceptors were designed "instead to tackle the potential threat posed by short and medium- range attacks from outside the Euro-Atlantic area".
But Russia says installing such shields in countries on its doorstep is a threat to its security.
"Who will this system be against?" President Vladimir Putin's spokesman, Dmitry Peskov, questioned. "To begin with the explanation we were given was a potential rocket attack from Iran... Now we know the situation has changed dramatically."
How does the missile shield work?
The defence system allows on-shore sites and warships to shoot down enemy ballistic missiles while they are still in space.
The interceptor missiles are fired to hit missiles before they re-enter the atmosphere, stopping them well before there is any danger of causing any damage.
The US is believed to have spent $800m (£554m) on the site in Romania, where work began in 2013.
On Friday, another phase of the project will be launched in Poland with a groundbreaking ceremony at Redzikowo, near the Baltic Sea. Aegis missiles are to become operational there in 2018.