Background: Students of higher educational institution are at higher risk of substance abuse.rnCurrently, substance abuse is one of the most burning public health problems in Ethiopia. Again,rnthe increasing rate of university students who take drugs, the scarcity of rehabilitation andrntreatment program on substance abuse threatens the present and future image of Ethiopia.rnAlthough it has been known that this public health problem is a pressing issue, the real extentrnand magnitude of the drug abuse is not yet properly explored. Only little research is done so far.rnObjective: This study aims at assessing the magnitude of Mekelle University studentsâ€™ practicernof psychoactive substance abuse and their intention to stop.rnMethodology: Across sectional study design using mixed research method was employedrn(Quantitative, qualitative) during April 2011. After stratifying for batch and sex, simple randomrnsampling (lottery) was used to select 662 students. Snowball sampling technique also wasrnconducted. Data were gathered by annonymous self administer questionnaire. EPI Info versionrn3.5.1 and SPSS version 16.0 were used for cleaning and analysis. Binary and multiple logisticrnregressions were used to describe and associate the relevant variables. OpenCode 3.6 was used tornmanage qualitative data. Finally; thematic analysis was used to analize the data. CAGE-AID wasrnused to measure substance abuse.rnResult: The response rate was 90.8%. Most 68% of the respondents were male. The magnitute ofrnsubstance abuse was [95%CI: 20.1 (17.07, 23.48)]. The commonly abused substances werernalcohol [95%CI: 16.6 (13.82, 19.78)] followed by khat 14.8(12.14-17.82) and cigarette andrncannabis each were abused [95%CI: 8.8 (6.743, 11.29)]. It has also been identified thatrnsubstances abuse in males [AOR, 95% CI; 2.214 (1.071, 4.575)] were two times higher thanrnfemale respondents. In addition, those who started to abuse substance through peer pressurern[AOR, 95% CI 14.931 (6.824, 32.668)] were 15 times more likely to abuse substances asrncompared to those who did not. In contrast, the study showed that students from Law andrnGovernance [AOR, 95% CI .127 (.048, .335)] was less likely to abuse substances. Furthermore,rnproportion of intention to stop among abusers was 49.6%.rnConclusion and Recommendation: From this finding, it is possible to conclude that, substancernabuse is an urgent problem among undergraduate university students; however, their intention tornstop is high. Sex, religion, field of study, reason to start and initiation time are statisticallyrnsignificant factors. Generally, from this study suggests that further work is urgently needed; torndesign suitable policies, culturally and psychologically appropriate intervention packages.rnKey words: Psychoactive substance abuse, Intention to stop, Mekelle University