Abstract Despite the COVID-19 pandemic, influenza remains an important issue. Especially in community settings, influenza outbreaks can be difficult to control and can result in high attack rates. In April 2022, a large A(H3N2) influenza outbreak spread in the largest Italian drug-rehabilitation community. One hundred eighty-four individuals presented influenza-like symptoms (attack rate of 26.2%); 56% previously received the influenza vaccine. Sequence analyses highlighted a genetic drift from the vaccine strain, which may have caused the observed lack of protection.