Following his retirement, De Sisti pursued a coaching career, achieving his coaching badges in 1980, and becoming head coach of his former club Fiorentina later that year, narrowly missing out on the league title to rivals Juventus in 1982. He was forced to leave his job in 1985 after being diagnosed with brain abscess. He returned to football with Udinese later that year, for two seasons, and then entered into the Italian Football Federation as head coach of the Italian "Juniores" (1988–90) and Military squads (1990–91), winning a Military World Championship with the Italian Military side in 1991. He made a return to club football later that year, with Ascoli, being successively sacked in January 1992.