With an overall score of 98.95 out of 100, the 122-room boutique hotel came behind The Athenee Hotel and Four Seasons Hotel Bangkok in Thailand and Four Seasons Hotel Kuala Lumpur in Malaysia.
Set on a two-and-a-half-hectare site with 200 meters of frontage on the Huong (Perfume) River, the hotel was built in a colonial style.
The mansion at the heart of the hotel was built in 1930 as part of the residence of the French Resident Superior.
Its distinctive facade, long horizontal lines and nautical flourishes are hallmarks of the streamline modern school of art deco.
Rooms cost from VND5 million ($208) a night.
Thailand dominated the top 10 with five representatives, followed by Cambodia with two.
The results were based on votes of more than 240,000 readers who rated their travel experiences as part of the 2022 Readers' Choice Awards.
The awards are the longest-running recognition of excellence in the travel industry, recognizing the world's very best hotels, resorts and destinations.