Background: Reproductive health (RH) care is a set of methods, techniques and services that contribute to reproductive health and wellbeing by resolving reproductive health (RH) problems. Aim of the study: To evaluate the effect of different teaching methods in improving level of knowledge about reproductive health among female student Hadhramout University. Subjects and methods: The study was conducted in two colleges from Hadhramout University (College of Nursing & Girls) at Mukalla City, Yemen using a quasi experimental design. It involved 100 female students from Nursing and Girls Colleges from students were registered in the first grade during academic year 2014~2015. The data collection tools were an interview questionnaire composed of two parts: a- socio-demographic characteristics, and b-knowledge of students about reproductive health issues used at pre-post test to evaluate the improvement of students knowledge regarding reproductive health (RH) issues. The data collection lasted from November 2014~January 2015. Results: Showed that the total score of satisfactory knowledge about reproductive health (RH) issues; Puberty, Fertilization, STDs, Marriage, Family planning, FGM, and Feminine hygiene among intervention group students improved from (2%, 8%, 16%, 14%, 6%, 10%, and 16%) respectively in pretest, to (94%, 96%, 94%, 98%, 98%, 98%, and 98%) respectively in posttest, compared to slightly increase among self-learning group students from (8%, 20%, 22%, 58%, 34%, 36%, and 52%) respectively in pretest, to (10%, 28%, 26%, 60%, 40%, 46, and 58%) respectively in posttest. Highly statistically significant in total score of knowledge among intervention and self-learning groups after the program implementation (P = 0.000). Conclusion and recommendations: The different teaching methods intervention had a positive impact on increasing the female students awareness regarding to reproductive health issues among intervention group. The study recommends conducting health education services about reproductive health issues in every college, booklet about reproductive health issues should be available in every college in addition to every medical care services.