Substance use disorders in the united states recently reached epidemic proportions (Center for disease control and prevention) [2017].Substance abuse in society an estimated 600 billion annually from loss of productivity, health care utilization costs, and criminal justice cost (National institute on drug abuse 2016) .It affects the individual from all walks of life regardless of race, gender, geographic location, or socio economic status. Objectives of the study: To assess the level of knowledge among high school students regarding prevention of substance abuse. To find the association between knowledge score with selected demographic variables. Method: A descriptive survey approach was considered suitable for this study the aim of the study was to evaluate the knowledge of high school students regarding prevention of substance abuse. Research approach tells the researchers from whom the data is to be collected, how to collect and how to analyse the data. It also suggests the possible conclusion and helps the researcher in answering specific research question in the most accurate and efficient way possible. Research design is the overall plan for obtaining answer to the question being studied and handling some of the difficulties encountered during the research process. To accomplish the objectives of the study a descriptive survey was used to assess the knowledge towards prevention of substance abuse among high school students. Setting is the physical location and condition in which data take place. The study is conducted in a selected school in Mangalore. The population is high school students of a selected school in Mangalore that have one or more characteristics in common that are of interest to the researcher. Sample is subset of population selected to participate in research study. The sample for the present study was 30 male and female students from a selected school of Mangalore. Results: assessing the knowledge of high school regarding prevention of Substance abuse. The Discussion is described under the following heading. Description of demographic variable of high school students. Analysis of knowledge of high school students regarding prevention of substance abuse. SECTION 1: Description of demographic variable of high school students. 70% of students in the age group 14 years and 30% were in the age group of 15 years. 30% were Christians , 46.7% were Hindus and 23% were Muslims .23.3%of students parents are doing business , 76.7%were coolies, 6.7% are Professionals and 13.3% unemployed .70% of the Students get the knowledge regarding prevention of substance abuse from internet , 6.7%of them from newspaper 20%of students from teachers and only 3.3% get knowledge from other services. The results shows that the highest percentage (46.6% ), of the sample had an good level of knowledge whose score ranged between 14-20 and 23.35 % of the sample had poor knowledge.