Background: The objectives of the study were to assess awareness, opinions, and practices regarding electronic cigarette (e-cigarette) use, as well as factors associated with their use, among middle-school aged students from rural areas of Romania. Methods: The study sample included 748 middle-school students aged 13–14 years from 24 schools from rural areas situated in two counties from Romania, after receiving parental consent. A cross-sectional study using confidential questionnaires which assessed smoking-related behaviors, and also opinions and practices related to e-cigarettes use, was performed in 2019 among the participating middle-schoolers. Results: 96.3% of the middle schoolers have heard about e-cigarettes. A percentage of 72.7% of the smokers, 50.8% of the ex-smokers, and 15.4% of the non-smokers had tried e-cigarettes at least once in their life; 20.3% of the smokers, 4.8% of the ex-smokers, and 4.5% of the non-smokers reported using e-cigarettes in the last month. The results of multivariate logistic regression analysis pointed out that e-cigarette use at least once during lifetime was associated with having friends who tried e-cigarettes, having stronger beliefs that they can help quit smoking and that they are less dangerous than traditional cigarettes. The intention to use e-cigarettes in the next year and smoking behavior were also correlated with e-cigarettes experimentation, while no gender differences were found. Conclusions: The results underline the importance of having prevention programs and interventions concerning e-cigarettes consumption, since e-cigarettes consumption is spread among Romanian adolescents from rural areas.