The index closed 0.16 points lower after gaining 7.43 points in the previous session.
Trading on the Ho Chi Minh Stock Exchange decreased by 15% to VND11.355 trillion (US$447.3 million).
The VN-30 basket, comprising the 30 largest capped stocks, saw 9 tickers gained.
FPT of IT giant FPT Corporation saw a 2.7% growth, POW of electricity producer Petrovietnam Power Corporation rose 1.6% and BVH of insurance company Bao Viet Holdings was up 0.5%.
Fourteen blue chips fell. SSI of brokerage SSI Securities Corporation went down 1.2%, VHM of property giant Vinhomes slipped 1.2% and VRE of retail real estate arm Vincom Retail closed 1.1% lower.
Foreign investors were net buyers to the tune of VND355 billion, mainly buying FPT and TCB of private lender Techcombank.
The HNX-Index for stocks on the Hanoi Stock Exchange, home to mid and small caps, fell 0.27%, while the UPCoM-Index for the Unlisted Public Companies Market went down 0.10%.
Globally, Asian stocks fell on Wednesday and currencies were volatile as investors fretted over whether other countries could be targeted for tariffs under incoming U.S. President Donald Trump, a day after he pledged new levies on Canada, Mexico and China, Reuters reported.
MSCI's broadest index of Asia-Pacific shares drooped 0.3%. Taiwanese stocks lost 1.5%, while South Korea's KOSPI dropped 0.8%.
Japan's Nikkei declined more than 1%. The autos sector was the worst-performing industry group on the Tokyo Stock Exchange, dropping 3.6% as both the threat of tariffs and the drag of a stronger yen weighed on the profit outlook.
However, mainland Chinese blue chips recovered from early losses to rise by 0.7%, while Hong Kong's Hang Seng added 0.5%.