Purpose Few studies have compared the effect of Web-based eLearning versus small-group learning on medical student outcomes. Palliative and end-of-life (PEOL) education is ideal for this comparison, given uneven access to PEOL experts and content nationally. Method In 2010, the authors enrolled all third-year medical students at the University of California, Davis School of Medicine into a quasi-randomized controlled trial of Web-based interactive education (eDoctoring) compared with small-group education (Doctoring) on PEOL clinical content over two months. Students participated in three 3-hour PEOL sessions with similar content. Outcomes included a 24-item PEOL-specific self-efficacy scale with three domains (diagnosis/treatment [Cronbach alpha = 0.92; CI: 0.91-0.93], communication/prognosis [alpha = 0.95; CI: 0.93-0.96], and social impact/ self-care [alpha = 0.91; CI: 0.88-0.92]); 8 knowledge items; 10 curricular advantage/disadvantages; and curricular satisfaction (both students and faculty). Results Students were randomly assigned to Web-based eDoctoring (n = 48) or small-group Doctoring (n = 71) curricula. Self-efficacy and knowledge improved equivalently between groups (e.g., prognosis self-efficacy, 19%; knowledge, 10%-42%). Student and faculty ratings of the Web-based eDoctoring curriculum and the small-group Doctoring curriculum were equivalent for most goals, and overall satisfaction was equivalent for each, with a trend toward decreased eDoctoring student satisfaction. Conclusions Findings showed equivalent gains in self-efficacy and knowledge between students participating in a Web-based PEOL curriculum in comparison with students learning similar content in a small-group format. Web-based curricula can standardize content presentation when local teaching expertise is limited, but it may lead to decreased user satisfaction.