OBJECTIVE To assess self-medication practices and to evaluate the impact of obtaining medical knowledge on self-medication among medical and pharmacy students at Jordan University of Science and Technology. METHODS This was a cross-sectional study. A well-validated questionnaire that included 3 sections about self-medication was administered to the subjects after introducing the term "self-medication" verbally. RESULTS 1,317 students had participated in the study and were subgrouped according to their academic level into seniors and juniors. Compared to the general population rate of 42.5%, self-medication practice was reported by (1,034, 78.5%) of the students and most common amongst pharmacy students (n = 369, 82.9%) compared to Pharm.D. (n = 357, 77.9%) and medical students (n = 308, 74.4%) (p = 0.009). There was no significant difference between juniors and seniors (557, 79.1% vs. 477, 77.8%, p = 0.59, respectively). Headache (71.2%) and common cold (56.5%) were frequent ailments that provoked self-medication. Analgesics (79.9%) and antibiotics (59.8%) were frequently used to self-treat these aliments. Reasons for self-medication included previous disease experience (55.7%); minor aliments (55.3%); and having enough medical knowledge (32.1%). Medicines were used according to instructions obtained mainly from the leaflet (28.8%); pharmacist (20.7%); and university courses (19.7%). Senior students were more aware of the risk of self-medication than junior students. The majority of students frequently advise other people about self-medication (83.6%). CONCLUSIONS Self-medication was common among students irrespective to their level of medical knowledge. Obtaining medical knowledge increased the students' awareness of the risk of self-medication which may result in practicing responsible self-medication. However, medical teaching institutions need to educate students about the proper use of medicines as a therapeutic tool.