To design effective solution for the problem substance abuse, it is essential to understand its predictors and assess its prevalence, even though the prevalence is thought to be increasing; only little is known in any Ethiopian setting. The study revealed 47.6 % life time prevalence and 40.6 % current prevalence of substance use specifically 31.1 % Khat Chewers, 14.1 % Alcohol drinkers and 6.7 % cigarette smokers. Using logistic regression, male gender (p<0.001), being in the age group 19-29 (p=0.001), having substance user family (p=0.04), and having substance user friend (p<0.001) were found to be independent predictors of substance use. Substance use behaviors were associated with factors as age group, Male Gender, user family member and user friend. Substance use prevention programs directed at these groups are most likely to succeed in minimizing the prevalence.