The research-based pedagogical strategy of flipped classes has been shown to be effective for increasing student achievement and retention in postsecondary chemistry classes. The purpose of flipped classes is to move content delivery (e.g., lecture) outside of the classroom, freeing more face-to-face time for active learning strategies. The opportunity to engage in active learning with students can be a challenge for instructors of large classes (more than 100 students). Furthermore, there has been little discussion in the chemical education literature to provide instructors with detailed descriptions of successful implementations of flipped classes combined with active learning in large classes. To this end, this report provides a comprehensive description and evaluation of a coordinated implementation of flipped classes with peer-led team learning (PLTL) for second-semester general chemistry with class sizes greater than 200 students. This approach is described as “Flipped PLTL”. This report includes details about creation of videos for flipped instruction, class structure, and the recruiting and training of peer leaders. The purpose of this paper is to provide an example of flipped classes with PLTL that can guide other instructors who wish to implement these pedagogies in large classes.