Bugiardini was an independent artist by 1503, the year in which the joined the Florentine painters' confraternity the Compagnia di San Luca and formed a business partnership with Mariotto Albertinelli.
In 1508, Bugiardini, Agnolo di Domenico del Mazziere, Francesco Granacci and other artists were called to Rome to assist Michelangelo with the Sistine Chapel ceiling, but their services were quickly rejected and the team was sent back to Florence.
According to Vasari, Michelangelo designed most of the figures in Bugiardini's large Martyrdom of Saint Catherine (1530–40) in the Rucellai chapel at Santa Maria Novella in Florence.
Bugiardini has long been criticized as a mediocre talent incapable of understanding the formal principles of Michelangelo, Raphael, Leonardo and Fra Bartolomeo, all major influences on his work.
The Virgin and Child with Saints Mary Magdalene and John the Baptist (circa 1523) at the Metropolitan Museum of Art, widely regarded as one of Bugiardini's most successful creations, is so refined that it was once considered to be by Fra Bartolomeo.