Dean's legacy comes almost entirely from his research into fluoridation. At the urging of Dr. Frederick McKay and others concerned with the brown-staining of teeth in certain regions of the country, Dean was asked to make this his first assignment at the Institute in 1931. Dean was part of a team that focused on determining optimal concentrations of fluoride in drinking water that would only cause minimal and mild mottled enamel on the teeth, while at the same time precipitating lower rates of dental caries. In 1934, as part of this work, Dean published an index to categorize the severity of dental fluorosis. In 1939 he reported on children who grew up in 4 nearby Illinois towns: “These differences are so great that little comment seems necessary. The 2,718 surfaces in the children showed only 0.59 carious lesion per 100 surfaces. In the 2,814 tooth surfaces of the children there were 8.9 carious lesions per 100 surfaces, or 16 times as much…” The August 1, 1943 Journal of The American Dental Association referenced Dean as acknowledging the difficulty of identifying an optimal concentration with the following quote, "The same amount of fluorine that causes a mild toxic reaction in one individual may cause a severe reaction in another. In other words we are dealing with a low-grade chronic poisoning of the formative dental organ in which case some individuals may show a more severe reaction than others having a comparable fluorine intake." Dean's professional life was spent searching for an optimal level of fluoride that would prevent tooth decay yet avoid staining or otherwise damaging teeth. In 1952, McKay and Dean were presented with the Albert Lasker Award for Clinical Medical Research by the American Public Health Association for their work with fluoride.
Later life
After his retirement, Dean joined the American Dental Association as Secretary of its Council on Dental Research. In this role, he continued to advocate and defend the addition of fluoride to public drinking water. He was frequently called to speak on the subject in the United States and abroad, mostly to refute the arguments of those who opposed water fluoridation. In 1949, he was presented with the Gorgas Medal from the Association of Military Surgeons of the United States. He died in 1962, after a long battle with asthma and emphysema. The International Association for Dental Research has an award named after Dean, called the H. Trendley Dean Memorial Award, recognizing meritorious research in epidemiology and public health.