One of the demanding tasks for English for Specific Purposes (ESP) classes at Can Tho University of Medicine and Pharmacy (CTUMP) is making a presentation. This paper aimed to examine students’ perceptions of towards making ESP presentation and find out difficulties that they might encounter in making ESP presentation. And for the methodology, the cross-sectional descriptive study was carried out with 540 second-year students. The data were collected by the use of questionnaire. The findings revealed 72.1% students’ positive perceptions towards making ESP presentation as well as significant problems including a lot of ESP vocabulary in materials for presentations, difficulties in memorizing the presentation contents, lack of confidence, self-study and teamwork skills and other problems related to facilities.