Aim: To evaluate the educational effectiveness of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduate medical trainees compared to a traditional lecture-based course of equivalent content. Methods: We conducted a cluster randomized controlled trial to compare a clinically integrated e-learning EBM course (intervention) to a lecture-based course (control) among postgraduate trainees at foundation or internship level in seven teaching hospitals in the UKWest Midlands region. Knowledge gain among participants was measured with a validated instrument using multiple choice questions. Change in knowledge was compared between groups taking into account the cluster design and adjusted for covariates at baseline using generalized estimating equations (GEE) model. Results: There were seven clusters involving teaching of 237 trainees (122 in the intervention and 115 in the control group). The total number of postgraduate trainees who completed the course was 88 in the intervention group and 72 in the control group. After adjusting for baseline knowledge, there was no difference in the amount of improvement in knowledge of EBM between the two groups. The adjusted post course difference between the intervention group and the control group was only 0.1 scoring points (95% CI -1.2-1.4). Conclusion: An e-learning course in EBM was as effective in improving knowledge as a standard lecture-based course. The benefits of an e-learning approach need to be considered when planning EBM curricula as it allows standardization of teaching materials and is a potential cost-effective alternative to standard lecture-based teaching.