Abstract Background Sexually transmitted infections are a major public health problem, and their number is increasing in Italy. However, affective sexuality education is not yet part of the curricula. Therefore, a project entitled ESPRIT was launched, involving 3 regions (Friuli-Venezia Giulia, Lazio and Sicily), the IRCSS ‘Burlo Garofolo’ and the Istituto Superiore di Sanità, and implemented with the technical and financial support of the Ministry of Health - CCM. Methods A multicenter prospective intervention study was designed involving public upper secondary school students (grade 10-11). All target groups completed a KAP (knowledge, attitude, practice) questionnaire before and after participation in the educational intervention to measure its effectiveness. The questionnaires from the first phase were collected between January and April 2024, and the results were analyzed using R statistical software. Results The analysis of the overall results (463 students in total; female 58%, male 39%, other 2%; FVG 49%, Lazio 25%, Sicily 26%) showed that the group of upper secondary school students, targeted by peer education answered the knowledge part correctly by 56.6±13.8% on average. Applying the Kruskal-Wallis test showed that the percentage was significantly higher for females than males (p-value=0.005) and for licei students compared to technical and vocational schools (p-value=0.000). In terms of to attitudes, only 17% of students talked at length about sexually transmitted infections, and in 86.6% of cases, the interlocutors were friends or peers. Conclusions The results of the first phase show differences between the sexes and between the different types of educational institutions. The current level of knowledge still leaves much room for intervention and improvement. Analyzing the results of the follow-up phase will allow us to understand the effectiveness of the peer education intervention. Key messages • Adolescents’ knowledge of sexually transmitted infections needs to be improved. • Gender and the type of school attended affect the level of knowledge.