Background: HPV is the most common sexually transmitted disease in many regions of the world. 15% was found in women aged 15-19 years but the highest incidence of infection from HPV can be found in sexually active adolescents: between 50% and 80% of them catch the infection within two to three years from their first sexual relationship. Methods: A community randomized trial regarding HPV infection and HPV vaccination, and sexual health was carried out, in a sample of secondary school students. Peer education intervention was carried out and 2 follows-up were carried out after the educative intervention to evaluate the effective outcomes in a 1-year follow up of the effect of peer health education on primary prevention knowledge, attitude and behaviour towards HPV. Results: The sample of 900 students, with age of 16.6 ± 1.4 ds, 34.4% of which have sexual relationships. 64.6% of students in the experimental group said that they were aware of HPV, 83.4% were aware of how it is transmitted and 71.1% knew HPV vaccination, 54.7% perceived the level of danger with significant gender-related differences the percentages increased at T1. At T0, 14.1% of females were vaccinated: T1 they were 17.5% and 19.2% at T2. The main factors associated with the students’ propensity to vaccination were: having at least one sister; being in favor of vaccinations in general; knowing that the vaccine is aimed at preventing cervical cancer; and being aware that they could be infected by HPV. Conclusions: The study carried out highlights important differences between the experimental group and the control group in terms of knowledge but, most importantly, in terms of behaviour and it proves how the application of new educational methods based on the involvement of youngsters right from the initial stages of the project can help them to change their behaviour and maintain it in time