Audience Response Systems (ARSs) may enhance short-term knowledge retention. Long-term knowledge retention is more difficult to demonstrate. According to previous studies, ARS questions requiring application of knowledge or peer interaction are more effective in maintaining student attention. The purpose of this study was to determine if peer discussion or individual-knowledge questions enhance short- and/or long-term knowledge retention. Third-year veterinary students responded to ARS questions posed in individual knowledge (n=3 questions) and peer discussion (n=3 questions) format from six different instructors. To test short-term memory, the same questions were delivered during the course examination (within 21 days). To test long-term retention, these questions were posed during a retention exercise (four months later). On the course examination, students had a higher (p<.01) probability (±SE) of correctly answering ARS individual-knowledge questions (93.8 ± 1.8%) compared to novel (previously unseen, non-ARS control) course examination questions (87.5 ± 3.1%), but the probability of correctly answering examination questions previously posed using ARS peer discussion format (89.5 ± 3.0%) did not differ from individual knowledge or novel examination questions. The positive impact of ARS-knowledge questions was not maintained through the retention exercise. Neither individual knowledge (70.5 ± 6.4%) nor peer-discussion questions (67.5 ± 6.9%) performed better on the retention exercise than the questions that appeared only on the course examination (68.6 ± 6.1%). Curricular strategies that emphasize content review may be more powerful than strategies that strengthen initial learning for long-term content retention.