Leonardo's relations with the "Spedale" of Santa Maria Nuova are documented not only in his will, but also at various moments in his life. Here he not only had his bank, but also deposited cases of printed books, manuscripts and books of drawings. And it was here that he conducted his anatomical studies.

An autograph folio by Leonardo in the Windsor Royal Library confutes the legend according to which he robbed corpses to use them secretly as models for his drawings. It is Leonardo himself to report how he acted in full legality, and showing great humanity: «And this old man, a few hours before he died, told me he was over a hundred years and that he felt no pain in his body, only great weakness. And so, sitting up in bed in the Hospital of Santa Maria Nova of Florence, without any movement or sign of any mishap, he passed away. And I conducted anatomy on him, to find the cause of such a gentle death: the which I found to consist of a lack of blood in the arteries that nourish the heart and the other lower members, which I found very arid, worn and dry. I described this anatomy very diligently and easily, since the body had no of fat nor humours, which severely hinder recognition of the parts. The other dissection was that of a child of two, in which I found everything the opposite that of the old man». On the recto of this same folio (19027r, dating from 1506-8) Leonardo notes: «Drew the arm of Francesco the illuminator, which shows many veins.»

A tradition, consisting more of legend than documented history, tells of great stone basins in the undercroft of the Hospital that were used for the cadavers studied by Leonardo. Although this is a strongly evocative image, in the current state of knowledge it still remains to be proven.

The Renaissance artists/engineers already felt the problem of protecting their technological knowledge, inventions and "secrets" with what are now called patents. One example can be seen in the request made by Brunelleschi to the Florentine Signoria in 1421 to protect the invention of the "badalone", a boat designed by him to transport slabs of marble from the quarries at Carrara to Florence.

Around 1506, in the Codex Leicester (f. 15A-22v), Leonardo asked himself, «Why do I not write about my method for remaining under water?… I do not publish or divulge it due to the evil nature of men, who would use it for assassination at the bottom of the sea ….». This passage shows an ethical sense of secrecy that seems to contrast with the notes on a youthful folio in the Codex Atlanticus, where Leonardo shows himself primarily jealous of his secrets («Do not teach and you alone will excel»). Here he was in fact describing the way to sink enemy ships by surprise, with divers who would use Brunelleschi's screws, the same employed on the construction site of Santa Maria del Fiore («Bring one of the 3 iron screws from the works of Santa Liberata»). In this way Leonardo thought of managing to capture enemy commanders so as to collect a ransom, but with a written agreement stipulated to ensure the gain: «Take the commanders in your own way and secretly, with many bonds, put them ashore, but first make a pact through an instrument [a notarial deed], that half the reward will be yours, freely and without any exception».

«Remember the welds used to weld the ball over Santa Maria del Fiore. Of copper impressed in stone like the triangles of that ball». In this note in Ms. G (f. 84v), datable around 1515, Leonardo recalled a technological experience from his youth, carried out at Verrocchio's side on May the 27th, 1472.

This was the gilded sphere placed atop the lantern that crowned the masterpiece of Brunelleschi.

«The wool merchants' guild should make the canal, and take the profit from it, said canal passing through Prato, Pistoia, Serravalle». As may be deuced from this note in the Codex Atlanticus (1107r), dating from around 1495, Leonardo thought that the Arte della Lana, the wool merchants' guild, would assume the costs and collect the earnings of the canal into which he planned to deviate the waters of the Arno.

In Florence, especially in the quarters of San Frediano and Santa Croce, there are many place names deriving from the activities controlled by the rich and powerful Arte della Lana: Via and Piazza del Tiratoio (drying shop), Via dei Tessitori (weavers) Via dei Cardatori (carders), and Corso dei Tintori (dyers), which runs from the National Library to Via de’ Benci.

Silk-working instead had been controlled by a powerful mercantile guild since the late 12th century, the recollection of which has survived thanks to the work of the Antico Seticio Fiorentino (ancient Florentine silk manufactory). This manufactory, established near the end of the 18th century at the initiative of such noble families as the Gheradesca, Corsini and Guicciardini, was originally located in Via dei Tessitori. It is situated today in Via Bartolini 4, and is owned by the Pucci family. It still works with a weaving machine that, according to ancient tradition, derives from the drawings of Leonardo, and still produces damasks, brocades and other rare and precious fabrics using techniques dating from the 15th and 16th centuries.

In the Codex Atlanticus (f. 699b-v), between 1506 and 1508, Leonardo recalls an «ocel della commedia», the automaton of a bird appearing in a theatrical performance. This brings to mind the ancient engineer Architas of Taranto, sometimes called the "Greek Leonardo" (428 - 347 B.C.), and Villard de Honnecourt (13th century), as well as the "dove", an element in that complex pyrotechnic pageant of Renaissance origin held every Easter in Florence, in Piazza del Duomo. Other famous figures in the Florentine Renaissance were also interested in the problems of theatrical set design. Memorable, in fact, were the theatrical/technical sets designed by Brunelleschi for the churches of Santissima Annunziata, Santa Maria del Carmine and San Felice in Piazza.

Undoubtedly, Leonardo had in mind these elaborate theatrical sets when he designed the complex mechanical devices for the staging of Bernardo Bellincioni's Paradise Festival, presented in Milan in 1490. Sophisticated mechanisms operated by counter-weights were used instead for Poliziano's Orpheus, whose stage sets included a "mountain that opens" from which emerged Pluto. The direct influence of the mandorla [almond], designed by Brunelleschi to allow an announcing angel to appear in a corner of the church of San Felice in Piazza, seems to be at the origin of the scenography for Baldassarre Taccone's Danae, mention of which is found on a folio in the Metropolitan Museum of New York, dating from around 1496.

Leonardo recalls Monte Ceceri and Fiesole in his Codex on the Flight of Birds: first for having sighted there a cortone "bird of prey" on March 14, 1505 or 1506, and again for his prophecy on human flight from Monte Ceceri. In the clearing at the top of this mountain, the prophetic words of Leonardo are inscribed on a pillar: «The great bird will take its first flight on the back of Mount Cecero, filling the universe with amazement, filling with its fame all writings and bringing eternal glory to the nest in which it was born.»

Below Monte Ceceri, at the curve known as Il Regresso, on the wall that runs along the provincial road connecting Fiesole to Florence, another plate recalls the same Leonardian project. Legend has it that one of his followers, Zoroastro from Peretola, tried to fly from Monte Ceceri, but the attempt ended in a disastrous fall.

Leonardo's first drawing of a flying machine dates from his first Florentine period, around 1480.