Over the last decade, online learning has seen considerable growth, with this being supported by the rapid development of the Internet and other technologies. It is therefore vitally important for academics and practicians to evaluate the effectiveness of e-learning, so they can enhance the learners' acquisition of knowledge and the performance of educational organizations. This study was conducted within this context with the aim of assessing the effectiveness of e-learning and investigating its main predictors, as well as the moderating role of learners' self-efficacy. A conceptual model was developed and used to test the relationships that e-learning effectiveness has with the online interactions between learners and course content, learners and other learners, and learners and the instructor. In addition, self-efficacy with Internet and computer technologies and online communication was also examined as a potential moderator. To test our research hypotheses, we conducted a quantitative empirical study through a web-based survey, with structural equation modeling being used to analyze the data. Online interactions between learners and course content and between learners and the instructor were both found to be significant predictors of e-learning's effectiveness. In addition, self-efficacy was found to play a significant moderating role but only in the dimension of online communication. This paper makes a novel contribution to the existing literature by investigating e-learning's effectiveness as a bi-dimensional concept covering net benefit and e-learner satisfaction. In addition, this study adds to our understanding of online learning by investigating the moderating role that students' self-efficacy can play in terms of both the communicational and technological dimensions. For institutions of higher education, the findings of this study provide some constructive insights and useful recommendations for improving the effectiveness of e-learning systems.