Introduction: Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) are among the most complex health problems of the 21 st century. Young people aged 15-24 years are the HIV/AIDS at risk group. The objective of this study was to evaluate the effectiveness of an educational interventional program on knowledge on HIV/AIDS among adolescent students of higher secondary school in Kathmandu, Nepal. Methods: The study was the pre test-post test experimental study design with an experimental and a control group conducted in the randomly selected eighteen higher secondary schools. The intervention, educational package on HIV/AIDS, was provided to all grade twelve students in the intervention group from 1st September, 2017 to 2nd January, 2018. In total, 321 from the intervention group, and 283 from the control enrolled at baseline and over 95% of these were followed up at posttest. The data were collected from self-administered questionnaires in English version and analyzed by using independence t-test and paired t-test. Results: Overall pretest knowledge of both intervention and control groups was comparable with 27.58 ± 4.05 and 28.53 ± 3.77 mean ± standard deviation respectively. But statistical analysis showed significant higher knowledge (P = 0.03) among control group. After the educational intervention, the mean knowledge score of control group increased by only 0.47, whereas the same score increased by 11.57 and reached 39.15 ± 3.7 in post-test for intervention group. The difference in post-test score was statistically highly significant (P < 0.001). The finding indicates that the educational intervention was effective in changing the HIV/AIDS knowledge How to cite this paper: