The work of Vitruvius was rediscovered by Florentines in the fifteenth century. One of his works that was particularly influential on Brunelleschi was De architectura, the only treatise on architecture left from antiquity. In particular, Brunelleschi’s work shows that he was influenced by Vitruvius’s writings on perspective, proportions, balance, and repetition.

Vitruvius proposed that a harmonious balance is key to accurate proportions. Brunelleschi incorporated such ideas about harmony into his design for many buildings. For example, his Santo Spirito and San Lorenzo in Florence all include evenly spaced columns and parallel arches.

Another influential subject that Vitruvius wrote a great deal about was rational proportions. Vitruvius helped develop defining aspects of classical architecture, such as the use of repeating units of measurement to determine the proportions of a space. For example, this technique is evident in the flooring of the Pantheon in Rome. Brunelleschi applied this Vitruvian understanding of rational proportions to many of his famous works, such as his Ospedale degli Innocenti, which is modeled on a cube for equal distance and depth between features.

In addition, Vitruvius's teachings on linear perspective also had a profound influence on Brunelleschi. The classical teachings on perspective gave Brunelleschi the mathematical knowledge to properly execute his Duomo in Florence.