Peer Instruction (PI) is a vibrant instructional strategy, used successfully for over two decades in undergraduate physics and mathematics courses. It has had limited use and few publications in medical education. This 12 TIPS provides a focused review on the evidence supporting its use in higher education and rationale for its wider adoption in medical education. The authors detail important steps for its implementation with large classes. Based on several years of experience with PI in a US allopathic medical school, they feel that PI attends to core principles from the science of learning and provides students and faculty with immediate feedback on learning. It is also adaptable to on-line synchronous administration.