He worked with Marco Zanuso and Eero Saarinen before establishing a 25-year business partnership with Henry Dreyfuss from 1956 until 1981.

Convinced that so-called ‘modern’ furniture designers were not, in fact, exploiting technology to its fullest potential, Diffrient became one of the earliest experts of modern ergonomics. He has spent much of his career systematically researching how the user interacts with his surroundings and incorporating his findings into practical designs.

The chair collections he designed for Knoll in 1980 were early examples of seating thoroughly informed by anatomical research and quantitative studies of workplace behavior. The chairs responded to the human body ― increasing comfort and ensuring user well-being.

Diffrient has since established his own studio in Connecticut. The winner of countless design awards, he has also served as chair of the International Design Conference in Aspen, Colorado, an adjunct professor of Design at UCLA, and a visiting critic at the Yale School of Architecture.