Medvedev said Russia remains open to discussions on the shield, which Russian officials say would harm the country's own deterrents to attacks, but "time is running out," RIA Novosti reported.
"The door is not closed for talks on missile defense," Medvedev said during a Euro-Atlantic security forum in Moscow.
Negotiations between Russia and NATO members on the U.S.-led missile defense system have been stymied by reluctance by the alliance to provide Russia with legally binding guarantees that the shield will not be used against it.
The United States said the shield would protect Europe against attacks by "rogue states" such as Iran and North Korea, but Russian officials have expressed concern the defense system could eventually be used to neutralize Russia's nuclear deterrent.
"Why should we believe that this new European missile defense is not targeted against us?" Medvedev said. "They keep telling us 'this system is for you,' but how should we use it?"