After getting Isabella into Rosanna Calvierri's school, Guido discovered it was not what it seemed. In 1580, he met the Eleventh Doctor following a failed attempt to get his daughter back, and the two became allies. Guido feigned another attempt as a distraction to let the Doctor gain entry to the school. Later he explained to the Doctor he had tried an underground passageway, but was blocked by a trap door. He offered to use the gunpowder he took from the shipyards while working on warships, but the Doctor refused.

When their plan failed again and Isabella was executed, the group met in Guido's house to plan their next act. The house was attacked by all the female Saturnyn converts, and while the Doctor, Amy and Rory escaped, Guido remained behind to avenge his daughter. He led the converts to his gunpowder, shouted, "We are Venetians", and set light to it. The explosion killed everyone in the house, and ultimately doomed the Saturnyn race to extinction. (TV: The Vampires of Venice)