Background: Adolescent reproductive health problems are a great threat to adolescent’s warfare and such problems are associated with inadequate knowledge. In Eritrea, as adolescent reproductive health is not given much attention the knowledge is expected to be poor, which could lead adolescents to become victims of adolescence related reproductive health problems and limit their opportunity to build a better future. Therefore, this study was carried out with the aim of investigating the reproductive health knowledge, attitude and practice among secondary school students in Asmara, the capital of Eritrea. Methods: A cross sectional study design was conducted on 428 adolescent high school students with the age range of 14 to 19 years. Sample size was determined by using a single population proportion formula. Initially, population size of each school and each grade was taken and proportional sample size was determined from each school and then from each grade. The list of students was used and participants were selected using simple random sampling. Data was collected through a structured self-administered questionnaire. Descriptive and inferential analysis were made using SPSS (version 22). Statistical significance level was set at P<0.005.Results: The median age of the study participants was 15 (IQR=2), in which 88.8% were between age of 14 to 16 years with 53% of them being females. The level of knowledge of the students regarding RH was low, with moderate to good attitude. Sexual practice was very low (3.5%) with usage of 86.7% of contraceptive use. Meanwhile, the usage of sexually explicit material was relatively higher (53%). Conclusions: Reproductive health knowledge was low almost in all variables. Meanwhile, significant number of students are already engaged in heterosexual romantic relationships and use of sexually explicit material. Adolescents need to be knowledgeable about themselves and the people they relate to, need sound information about the physical, psychological and social changes that take place through childhood to adolescence.