The aim of this paper is to determine gender differences as regards adolescent sexuality, in order to improve the adjustment of prevention programmes to boys' and girls' specific needs. Data were collected as part of the Swiss Multicentric Adolescent Survey on Health. Anonymous questionnaires were distributed in school classes among a national representative sample of about 9,300 adolescents (15 to 20 years old). About 45% of the total sample reported a previous sexual experience. Differences between boys and girls were identified by means of bivariate and multivariate analyses. A higher proportion of Swiss girls report intra-family discussions about sexuality, having had a previous sexual experience, having sexual intercourse regularly, having had only one partner, and using contraception regularly. A higher proportion of Swiss boys report positive attitudes towards condoms and using condoms regularly. Variables independently associated with the occurrence of first sexual intercourse before 15 years old also show gender differences, notably as regards health behaviours and social adjustment. The findings suggest that prevention programmes should emphasize, among boys, responsibility in contraception and the need for protection in situations of multipartnership, and among girls, a positive attitude towards condom use and an increased familiarity with condoms presented both in a perspective of contraception and prevention of STDs.