The 800-bed Brunel Building opened in May 2014, to provide services (including Accident and Emergency), which transferred from Frenchay Hospital in advance of its closure.

[5] Notable former medical staff include Grace M Westbrook, matron from 1958, who was the first practising nurse to be elected chair of the Staff Side of the Nurses and Midwives Whitley Council,[6] and Geoffrey Tovey, serologist and founder of the UK Transplant Service, which was formed in 1972 and was initially based at the hospital.

[10] Called the Brunel building, it would have 800 beds, 24 operating theatres, patient gardens, a public square, a helipad and visitors' multi-storey car park.

[15][16] The extension includes a new multi-storey car park for patients and visitors, a cycle centre with storage for 300 bikes, more shops, changing and shower facilities for staff and a community arts space.

[17] Following the 2014 opening of the Brunel building, there was a shortage of parking spaces owing to high demands from visitors, patients, and staff.

[20] In June 2024, Anne, Princess Royal was admitted to Southmead Hospital after sustaining concussion and minor head injuries on her Gloucestershire estate, believed to have been caused by a horse.