Washington's ban on US citizens traveling to North Korea came into force on Friday, with the two countries at loggerheads over Pyongyang's weapons ambitions.
The measure was imposed following the death of student Otto Warmbier in June, a few days after the 22-year-old was sent home in a mysterious coma following more than a year in prison in the North.
On its website the State Department said it took the decision due to "the serious and mounting risk of arrest and long-term detention of US citizens".
Three Americans accused of various crimes against the state are behind bars in the North, which is engaged in a tense standoff with the Trump administration over its banned missile and nuclear weapons programmes.
Exemptions to the travel ban are available for journalists, Red Cross representatives, those traveling for humanitarian purposes, or journeys the State Department deems to be in the national interest of the United States.
But NGOs working in the North privately express concerns about how the process will function and the potential impact on their work. A few remaining US citizens in the country left on Thursday, reports said.
Americans represent around 20 percent of the 5,000 or so Western tourists who visit the North annually - although that is expected to fall significantly this year because of the wider tensions as well as the ban - with standard one-week trips costing about $2,000 (1,700 euros) and budget journeys about half that.