This study aimed to measure the prevalence of Problematic Internet Use (PIU) among high school students and to identify factors associated with PIU underlining gender differences. The students filled a self-administered, anonymous questionnaire collecting information on demographic characteristics and patterns of Internet use. Multiple logistic regression analysis was performed to identify factors associated with PIU in the overall sample and by gender. Twenty-five schools and 2022 students participated in the survey. Prevalence of PIU was 14.2% among males and 10.1% among females. Males 15-year-olds and females 14-year-olds had the highest PIU prevalence that progressively lowered with age among females. Only 13.5% of pupils declared parents controlled their Internet use. The sensation of feeling lonely, the frequency of use, the number of hours of connection, and visiting pornographic websites were associated with the risk of PIU in both genders. Attending vocational schools, the activities of chatting and file downloading, and the location of use at Internet point among males, and younger age among females were associated with PIU, whilst information searching was protective among females. PIU could become a public health problem in the next years. The physical and mental health consequences should be studied.