Court records of 1476 show that Leonardo and three other young men were charged with sodomy, and acquitted. From that date until 1478 there is no record of his work or even of his whereabouts, although it is assumed that Leonardo had his own workshop in Florence between 1476 and 1481.

Professional life of Leonardo da Vinci, 1476–1513

Leonardo da Vinci was commissioned to paint an altarpiece in 1478 for the Chapel of St Bernard and The Adoration of the Magi in 1481 for the Monks of San Donato a Scopeto. This important commission was interrupted when Leonardo went to Milan.

In 1482 Leonardo, who according to Vasari was a most talented musician, created a silver lyre in the shape of a horse's head. Lorenzo de’ Medici sent Leonardo, bearing the lyre as a gift, to Milan, to secure peace with Ludovico il Moro, Duke of Milan. At this time Leonardo wrote an often-quoted letter to Ludovico, describing the many marvellous and diverse things that he could achieve in the field of engineering and informing the Lord that he could also paint.

Leonardo da Vinci continued work in Milan between 1482 and 1499

He was commissioned to paint the Virgin of the Rocks for the Confraternity of the Immaculate Conception, and The Last Supper for the monastery of Santa Maria delle Grazie. While living in Milan between 1493 and 1495 Leonardo listed a woman called Caterina among his dependents in his taxation documents. When she died in 1495, the list of funeral expenditure suggests that she was his mother.

He worked on many different projects for Ludovico, including the preparation of floats and pageants for special occasions, designs for a dome for Milan Cathedral and a model for a huge equestrian monument to Francesco Sforza, Ludovico's predecessor. Seventy tons of bronze were set aside for casting it.

The monument remained unfinished for several years, which was not unusual for Leonardo. In 1492 the clay model of the horse was completed. It surpassed in size the only two large equestrian statues of the Renaissance, Donatello's statue of Gattemelata in Padua and Verrocchio's Bartolomeo Colleoni in Venice, and became known as the "Gran Cavallo."

At the start of the Second Italian War in 1499, the invading French troops used the life-size clay model for the "Gran Cavallo" for target practice. With Ludovico Sforza overthrown, Leonardo, with his assistant Salai and friend, the mathematician Luca Pacioli, fled Milan for Venice, where he was employed as a military architect and engineer, devising methods to defend the city from naval attack.

Leonardo da Vinci returned to Florence in 1500

Leonardo da Vinci and his household were guests of the Servite monks at the monastery of Santissima Annunziata and were provided with a workshop where, according to Vasari, Leonardo created the cartoon of The Virgin and Child with St. Anne and St. John the Baptist, a work that won such admiration that "men and women, young and old" flocked to see it "as if they were attending a great festival."

In 1502 da Vinci entered the service of Cesare Borgia, the son of Pope Alexander VI, acting as a military architect and engineer and travelling throughout Italy with his patron. He returned to Florence where he rejoined the Guild of St Luke on October 18, 1503, and spent two years designing and painting a great mural of The Battle of Anghiari for the Signoria, with Michelangelo designing its companion piece, The Battle of Cascina.

In Florence in 1504, Leonardo  was part of a committee formed to relocate, against the artist's will, Michelangelo's statue of David.

In 1506 Leonardo da Vinci returned to Milan. Many of Leonardo's most prominent pupils or followers in painting either knew or worked with him in Milan, including Bernardino Luini, Giovanni Antonio Boltraffio and Marco D'Oggione.

However, da Vinci did not stay in Milan for long because his father had died in 1504, and in 1507 he was back in Florence trying to sort out problems with his brothers over his father's estate. By 1508 he was back in Milan, living in his own house in Porta Orientale in the parish of Santa Babila.