This study integrated an in-house audience response system (ARS) in the human anatomy course over two years to determine whether students performed better on high-stakes examinations following exposure to similar interactive questions in a large lecture format. Questions in an interactive ARS format were presented in lectures via PowerPoint presentations. Students who chose to participate in the anonymous ARS sessions submitted answers via their personal wireless devices (e.g., laptops, smartphones, PDAs, etc). Students were surveyed for feedback. Student participation in ARS activities was greatest (65–80%) in the first lecture. The number of students who actively participated in ARS activities decreased over the next four sessions, and then slightly increased in the last two sessions. This trend was the same for both years. Use of the ARS did not dramatically enhance overall student performance on examination questions that dealt with content similar to content presented in the ARS sessions. However, students who scored in the lower quartile of the examination performed better on the examination questions after the ARS was implemented. Accordingly, our findings suggest that the effect of ARS to improve student performance on examinations was not uniform. The overall benefit of an ARS to enhance the lecture experience was confirmed by student surveys. Anat Sci Educ. © 2010 American Association of Anatomists.