Substance use has become one of the growing major public health and socioeconomic issues worldwide; it has dramatically increased, particularly in developing countries. [1-3] The analysis of substance use is complex, due in part to its varieties, degree of secrecy, health challenges and different legal connotations surrounding its use globally. The use of khat (Catha edulis), cigarettes, heroine, alcohol and other substances is a worldwide threat which especially affects young people. The World Health Organization (WHO) estimates that there are about 2 billion people worldwide who consume alcoholic beverages, of whom 76.3 million are affected by alcohol-related disorders. [4-8] It is estimated that 9% of the global population aged ≥12 years are classified as dependent on psychoactive substances. [9] Studies have confirmed that there is a growing epidemic of tobacco, heroine and alcohol use among adolescents in the developing world, especially in southern Africa and in sub-Saharan Africa as a whole. [6,10-12] Khat has been used in African countries for centuries as a mild stimulant. For most youths, chewing khat is considered a method for increasing energy and elevating mood in order to improve work performance. [13] The WHO report on substance use in southern Africa showed that negative consequences are common traits of substance use. [3,14] These include sexual violence (e.g. rape), physical violence, criminal activity, neglect of social responsibilities, disease, injury and loss of life. Harmful effects occur with any psychoactive substance use and early initiation has been found to be associated with an increased risk of developing addiction and adulthood dependence. [3,15] In general, it has been shown that the use of cigarettes, alcohol and other substances is a worldwide threat that affects young people. [3,16] In some parts of Ethiopia, such as Bale and Harar, khat chewing in communities in which smoking is common is seen as a social custom that dates back thousands of years. Many students also consider khat chewing as a method of improving their reading ability. However, no activity has been seen in the reduction of substance use. [17,18] While substance use is not new in research parlance, [1] the high level of ingenuity among young people (especially adolescents) that has resulted in numerous complex mixtures, experimentation and discoveries of new materials and volatile solvents (or inhalants) that can be drunk or inhaled with immediate intoxicating effect or other diverse consequences, [11] could make continuous research on this menace relevant. The prevalence of substance use varies from country to country and time to time. Regular updates on substance use and its associated factors could therefore hold significant input regarding appropriate and dynamic interventions towards reduction or eradication of substance use among adolescents, not only in southern Africa but also worldwide. [19,20] The present study therefore aims to assess the prevalence of substance use among adolescent in sub-Saharan Afri...