BackgroundUse of psychoactive substances (PAS) early in school age implies drug dependence in later life. Although no studies have been conducted on undergraduate students of Hawassa University, a few studies in Ethiopia have reported that alcohol, khat, and cigarette are the commonly abused PASs among young high school/undergraduate university students. Therefore, this study was designed to establish the prevalence of and predictors for PAS use among undergraduate HU Students.MethodsAn institution-based quantitative cross-sectional study using the self-administered WHO Model Core Questionnaire to collect information on use of various Psychoactive Substances (PASs) was conducted from June to July 2011. A multistage stratified sampling method was employed to select a total of 586 undergraduate HU students as study participants. Bivariate and multivariate logistic regression analysis were done to determine factors affecting PAS use.ResultsLifetime, past 12 months, and current prevalence rate for overall PAS were 53.6%, 45.7%, and 35.5% respectively. The study depicted that in the past 12 months of the study period 40.8% used alcohol, 20.3% chewed khat, 11.9% smoked cigarettes, and 0.9% used marijuana. The prevalence of other illicit PASs such as Ecstasy, lysergic diethylamide (LSD), cocaine, crack, heroin, solvents or inhalants and un-prescribed psycho active medications was found zero percent (0%). Having family members who used PAS, peer influence, being male, and living alone during school age were found to be positively associated with overall PAS use in the past 12 months.ConclusionThe prevalence of PAS use among undergraduate HU students is high. Designing effective strategies to reduce PAS use should be everyone’s priority.