Background Although blended learning has the potential to enhance the student experience, both in terms of engagement and flexibility, it can be difficult to effectively restructure existing courses. To achieve these goals for an introductory Pathology course, offered to more than 250 undergraduate students at UNSW Sydney, we devised a novel approach. Methods For each topic presented over 2–3 weeks, a single face-to-face overview lecture was retained. The remaining content that had previously been delivered as conventional lectures was converted into short (12–18 min) online modules. These were based on lecture slides with added animations/highlights, plus narration using edited excerpts of previous lecture recordings. The modules also incorporated interactive questions and review quizzes with feedback which used various question types. Modules were developed in PowerPoint and iSpring and uploaded to Moodle as SCORM packages. Each topic concluded with an interactive large-group session focussing on integration of the content, with in-class questions to which students could respond via the Echo360 Active Learning Platform (ALP). Overall, more than 50% of face-to-face lecture time was replaced by online modules and interactive large-group sessions. Quantitative evaluation data included usage statistics from 264 students and feedback via online survey responses from 41 students. Qualitative evaluation data consisted of reflective commentaries from 160 student ePortfolios, which were analysed to identify factors affecting learning benefits and user acceptability. Results All of the modules were completed by 74% of students and on average, 83.1% of students eventually passed the optional review quizzes. Notably, 88.4% of students responded to in-class questions during the integration and feedback sessions via the ALP. Student reflections emphasised that the modules promoted understanding, which was reinforced through active learning. The modules were described as enjoyable, motivating and were appreciated for their flexibility, which enabled students to work at their own pace. Conclusions In transforming this introductory Pathology course, we have demonstrated a model for the use of blended learning in large group teaching sessions, which achieved high levels of completion, satisfaction and value for learning. Electronic supplementary material The online version of this article (10.1186/s12909-017-1057-2) contains supplementary material, which is available to authorized users.