In Roma Leonardo engaged in studies on mirrors of great size and projects for draining the Paludi Pontine, swamplands that had been owned by Giuliano de’ Medici since 1515, a project he carried out during his stay in the papal city.

According to Vasari, his contemporaries viewed Leonardo's Roman sojourn as a time of decline in his art.

In October 1515, Leonardo made a brief visit to Florence, along with the papal court, to meet the new King of France, Frances I, establishing contacts that would become useful to him when, at the sudden death of Giuliano de’ Medici, he decided to settle definitively in France.

The last known date of Leonardo's stay in Rome is August 1516, when, moved by an old interest in Early Christian architecture, he took the measurements of St. Paul's Basilica outside the walls (Codex Atlanticus, f. 471r).