The volcano rumbled to life in 1995 and has forced several evacuations since. More than half of the British Caribbean island's 11,000-person population has left. In 1997, two eruptions killed 19 people and buried much of the south, including the capital, Plymouth.
The lava dome has grown to dangerous levels, reaching its highest point in recent times — 1,640 feet high and nearly a mile wide.
Scientists fear the dome's collapse could result in the destruction of homes along the volcano's north side. More than 300 people have been ordered to leave.
"I can't believe I have to leave everything behind," said 73-year-old Clarris Skerrit who returned to the island from London when she retired and bought her yellow house.
"I've put everything into this house," she said.
Like other evacuees, Skerrit covered her furniture, plates and clothing in plastic, and boarded up her windows. Fine silt from ash spewed by the volcano for days blanketed nearly deserted neighborhoods.
Dozens of residents were reluctant to go, but officials threatened to arrest anyone who didn't leave by 6 p.m., said James White of the Emergency Department.
Most of the 300 people in the danger zone left for the homes of friends or family, but some went to government shelters, where each family is given a room.
Evelyn and Joseph Irish had to abandon their second home to the volcano. In 1995, they were evacuated from the south side of the Soufriere Hills. Wednesday, they headed to a government shelter, but had to abandon their dogs because it didn't allow pets.
"It's really hard feeling so frustrated," said Evelyn Irish, 49. "It's hard to find who to blame."
The Soufriere Hills is the Caribbean's only active volcano on a populated island. Another 15 volcanoes in the region are considered dormant, with the exception of the underwater Kick 'Em Jenny Volcano near Grenada.
"We were hoping the dome would collapse away from the population but unfortunately it keeps growing," said scientist Peter Dunkley of the Montserrat Volcano Observatory.
The volcano has expelled clouds of black ash for more than a week, covering buildings, cars and trees across the island, part of the Leeward chain between Antigua and Guadeloupe.
The evacuation order came after scientists warned that the dome could collapse in pyroclastic flows that hurl rivers of hot ash, gases and rocks across several miles at high speeds. It also can produce mud flows, lightning and intense heat that can ignite fires.
"It's like waiting to go to the dentist," Dunkley said. "Although it's painful, it has to be done. No one wants a collapse, but it has to happen."
It was unclear if the collapse would involve a major eruption, and scientists offered little hope to weary islanders who have suffered through many evacuations.
This week's evacuation zone includes Old Towne, Isle's Bay, Waterworks, Happy Hill, and lower Friths, all declared off-limits until further notice.