Background: Chewing the leaves of the Qat plant (Catha edulis) for their pleasurable central stimulant effect is a habit that is widespread in Yemen and certain areas of East Africa. The use of the Qat leaves is believed to cause a variety of gastrointestinal and genito-urinary symptoms as well as sleep disturbance. We studied the subjective effects of chewing Qat leaves in human volunteers. Subjects and Methods: This prospective study included 1600 healthy adult male subjects who chewed Qat, and a similar number of 1600 subjects who never chewed Qat serving as control. Subjects in the Qat group chewed Qat for at least four hours daily for three successive days before answering a questionnaire. Results: The study revealed that the prevalence of gastrointestinal (GI) symptoms (epigastric bloating, belching and abdominal distension) and genito-urinary symptoms (weak stream of micturition, post-chewing urethral discharge) were significantly higher (P<0.0001) among Qat-chewing subjects than controls. Similarly, central nervous system (CNS) symptoms such as anorexia, insomnia (delayed bedtime), late wake-up the next morning and low work performance the next day, were significantly higher in Qat chewers (P<0.0001). Stepwise multivariate logistic regression analysis revealed that GI symptoms which were significant in univariate analysis were no longer significant, whereas CNS and genito-urinary symptoms remained significant (P<0.0001). Conclusion: This study confirms that Qat chewing induces anorexia, weak stream of micturition, post-chewing urethral discharge and insomnia (delayed bedtime), which result in late wake-up next morning and low work performance the next day. These effects are believed to be caused by the central and peripheral actions of cathinone and cathine in the Qat leaves.