This paper provides an empirical analysis of the result of the referendum on constitutional reform held in Italy on 4 December 2016. The votes against (59.1%) won by a significant margin, with an unexpectedly high turnout at the polls and more than 33 million citizens voting. Using as a point of departure the polls carried out prior to and following the referendum, in which Italians said they were essentially in favour of the reform proposed by the prime minister, the essay focuses on the mistakes made by Matteo Renzi that discouraged Italians from voting Yes. These touch on all aspects of the referendum: 1) the parliamentary process, 2) its combination with electoral law, 3) institutional communication, and 4) his political analysis and strategic approach. The final section evaluates the effects of the referendum result on the Italian political system, emphasising the setback to reformism and the strengthening of the anti-system parties that support leaving the Euro (in particular the Movimento 5 Stelle).