After two attempts at opera, Manfredini devoted himself mainly to writing and teaching, also publishing a set of symphonies (1776) and string quartets (?1781).
When Pavel Petrovich became Emperor in 1796, he invited his former teacher, who arrived in September 1798, but took up no post and died in St. Petersburg the next year.
Manfredini's theoretical research Regole armoniche, o sieno precetti ragionevoli per apprendere la musica (Venice, 1775) has two parts, an introduction to the elements of music and to keyboard accompaniment.
The observations of Manfredini on the proper method of teaching singing aroused vigorous opposition from Giovanni Battista Mancini.
Manfredini composed numerous operas, as well as ballets, cantatas, sacred music (including a requiem), symphonies, string quartets, concertos, and chamber works.