Study objective To evaluate the prevalence of sexual activity and contraception methods used by Greek adolescents. To assess the effect of various factors in the decision making on sexual activity. Design A cross-sectional study design was applied. Setting-Participants The population (N = 1538) consisted of a random sample, stratified according to locality and population density, of 20 public junior high and high schools located in the urban district of Athens, Greece. Interventions Anonymous self-completed questionnaires were used to assess sexual practices, contraception methods, and factors affecting sexual activity choices. Measures Spearman association calculations and chi-square were used, while regression analysis models were also applied. Main Outcome We examined the sexual practices among Greek adolescents, and indicated the psychosocial factors that may influence adolescents' sexual behavior. Results 16% of the adolescents have had sexual intercourse, while the boy/girl ratio was 3/1 ( P < 0.05). Mean age of sexual debut was 14 ± 1.5 years. An additional 20% have had any other sexual experience at a mean age 13.5 ± 1.5 years. Although sexually active adolescents generally use condoms (90.6%), only 32% use them properly (at every and throughout sexual contact). At least half of them do not have adequate protection (no method used or unreliable methods applied), while 8.2% of the girls have used emergency contraception. Adolescents with unstable home environment (divorce, recent death, not living with mother) or sexually experienced peers, as well as those that seek sexual education from siblings or friends have higher possibilities of being sexually active. Conclusion Greek adolescents can be sexually active at a young age and they need sexual education on safe sex practices.