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The hospital opened on 1st December 1858 at 32 Soho Square as the Dental Hospital of London. The origins of all regulated and scientific dental practices can be found in the inception of the Dental Hospital and School. Before 1858 the dental profession had no regulation and anyone could set themselves up as a dental practitioner. This led to poor standards and a realisation of the need for proper training and an official qualification for dental practitioners. The Dental Hospital was established to achieve this and gained the backing of the Royal College of Surgeons to approve diplomas. The Dental School opened on 1st October 1859 to provide regulated, structured training for students in dental medicine. The hospital emphasised the need to regard dental medicine as connected to all other branches of medicine and to look at the wider picture when treating patients.
In 1911 the Royal Dental Hospital of London School of Dental Surgery became a school of the University of London and as well as their own Licence in Dental Surgery a University Degree in Dental Surgery was offered. This development allowed the Dental School to become involved in many of the developments in dental surgery that occurred in the early twentieth century. However the burden of debt did also mean that the School and Hospital did not develop as rapidly during this period as some of their competitors. The technological development of the Hospital was slowed down by the financial pressures and by the internal politics of the teaching and practice of Dental Surgery at this time.
The establishment of the NHS in 1948 saw the Royal Dental Hospital grouped with the Saint George's Hospital and Medical School, located on Hyde Park Corner and the Atkinson Morley in Wimbledon as the Saint George's Hospital Teaching Group. The School of Dental Surgery became a self-governing body, affiliated with Saint George's Hospital Medical School. The problems over space were still an issue. In 1957 plans to renovate the interior of the hospital to provide more space and better equipment were approved and the Hospital and School accomodation was reorganised, the School moved most of its non-clinical facilities into the newly acquired Ciro Club on Orange Street.
During the 1960's and 1970's the big issue was the transfer of the Dental School to Tooting with Saint George's Hospital and Medical School, which were to be rebuilt there. The Royal Dental Hospital was not at first happy with this and tried to delay the move, which was also held up by the Ministry of Health due to the finacial situation of the time. However Saint George's finally moved in 1975 and in 1976 the School of Dental Surgery's pre-clinical departments moved to Tooting. It was decided that the dental service required in Tooting was not that offered by the Royal Dental Hospital and the 1980's were spent preparing of the closure of the Hospital. The Dental School was amalgamated with the United Medical School of Guy's and Saint Thomas' Hospitals and the remaining dental services transferred to Tooting. The Royal Dental Hospital closed in 1985 and the site in Leicester Square was developed as the Hampshire Hotel.