The charity plans to close around 90 stores by the end of March 2027, and the remaining affected stores by March 2028.
It said it would share the locations of the stores earmarked for closure on its website once affected colleagues had been informed.
The charity also plans to reduce the central teams that support its retail arm.
Chief Executive Charmaine Griffiths acknowledged this would be a difficult time for colleagues and volunteers, thanking them for their contributions.
“Like most retailers, we are facing an exceptionally challenging trading environment,” she said.
“Cardiovascular disease remains one of the UK’s biggest killers and our priority is funding research to save lives.
“We must take the difficult step to close some of our shops to sustain retail’s important contribution to funding BHF’s groundbreaking research.”
The BHF said no single factor had led to its plans to close stores.
As well as its network of shops and donation points, the BHF has online retail channels including on its website and eBay.
It said it will continue to evolve its retail operations “to reflect changing customer shopping behaviours and donor habits”.
