- "Vittoria agli Assassini."
- ―Adriano's last words, 2012.[src]
On 5 September 2012, Adriano called the Assassin leader William Miles via telephone after Adriano tracked down his son, Desmond, who had been captured and taken to Rome by the Templars. Adriano offered to rescue Desmond with his team, but was stopped by William, who assured him that his mole in Abstergo Industries would keep Desmond safe.
Subsequently, on 14 September 2012, Adriano sent an e-mail to William informing him about a survivor of the Assassin team stationed in the Canadian town of Whistler, British Columbia, the other members of which had been killed by Templars on 12 September. According to the correspondence, which Adriano disguised with business terms, the survivor "left Whistler because he didn't want to be 'buried' in work there, like his colleagues."
Adriano e-mailed William again three days later, saying that the survivor's description of the man who led the Templar attack in Whistler fit that of "the guy who deceived a certain 'CEO' of [theirs], some 12 years ago", and that Adriano hoped to learn more during his meeting with the survivor the next day. On 19 September, Adriano received an e-mail from William, informing him that Lucy's team had gone dark, and that if he learned anything, he needed to call William immediately.
William then traveled to Europe, and Adriano was kept informed of his travel plans by Harlan Cunningham. When William arrived at the Florence hideout on 4 October, Adriano filled him in on what had been going on, and informed him that his condition had improved and he felt twenty years younger.
After William left and took over control of Lucy's team once she had been killed by Juno influencing Desmond, Adriano kept in contact with them until they were forced to go underground. On 24 October, Adriano sent a message in Morse code to Gavin Banks, informing him of the situation and ordering him to New York and prepare things for when William's team did eventually come out of hiding. Following this, William's team was able to escape Italy and reach Turin, New York, and as such, Adriano received an e-mail from William on 29 October. This email informed him that the team was waiting for Desmond to come out of his coma, in order for them to access the Grand Temple.
After William's team had entered the Grand Temple, Adriano learned that the Templars were attempting to hack into the Assassins' systems to track their location. On 27 November, he sent an e-mail to William stating that he had decided a "hostile takeover" was in order, and had his cell prepare for a raid on the Abstergo headquarters in Rome.
After the successful raid, the Assassins discovered on 29 November that the Templars had followed them back to their Florentine hideout. In an act of stubbornness, Adriano refused to leave, even though an attack was imminent. The following morning, a Templar strike team lead by Juhani Otso Berg attacked the hideout. When they reached the inner sanctum where Adriano was located, Berg challenged him. In response, Maestranzi defiantly declared in Italian "Victory to the Assassins!" and detonated a bomb, killing himself and the entire Templar strike team, save Berg who narrowly escaped. The explosion also destroyed the Assassins' files, preventing their contents from falling into Templar hands. Harlan, the only Assassin survivor, sent a message to William on 1 December confirming Adriano's death.
- Adriano was often called "old timer" by the other Assassins.
- Adriano died on 30 November, which was the same day of death as Ezio Auditore da Firenze.