Objectives: Electronic cigarettes (E-cigarettes) are relatively new devices developed for decreasing tobacco craving and reducing harm when they replace regular cigarettes. They are cheaper than ordinary cigarettes and have an enhanced taste and smell, so many individuals try to use them instead of ordinary cigarettes. Population knowledge and attitudes toward its benefits and harms have become a subject of research interest. The aim of this study is to explore the medical students’ beliefs, attitudes, and intended behavior about E-cigarettes at Tanta University, Egypt. Methods: A cross-sectional questionnaire-based study among medical students at Tanta University, Egypt, during March 2022 included 814 students. Results: About 66.8% of participants were male, with mean age 21.88 ± 1.59. About 17.4% were smokers, 74% were nonsmokers, and 8.6% were ex-smokers. About 78.6% of participants had heard about E-cigarettes. Media was the main source of knowledge in 57.9%. Two-thirds of them were interested in learning more about E-cigarette. Only 29.9% of students had moderate to high knowledge about electronic smoking (E-smoking). About 64.8% agreed that E-cigarettes may lead to conventional smoking. About 63.0% of the students agreed that it needs regulation at work and public places. While 57.6% consider it safer than regular cigarette, it is significantly higher in males and younger age <25 years. As a smoking cessation tool, 53.7% recommend it, especially female and younger age group. Older students aged ≥25 years had significantly higher negative attitude toward E-smoking (p = 0.001). Female and older students ≥25 years reported that they were extremely likely to counsel patients or their family members about E-cigarettes. Conclusion: Student knowledge about E-cigarette is still poor, and media ads are the main source of knowledge. Older students had a significantly higher negative attitude. It is important to increase awareness levels about E-cigarette, especially among school students and adolescents.