Direct-to-consumer (DTC) television advertisements present a number of facts about prescription drug risks and benefits in a brief time. This study assessed comprehension of information in three advertisements among 50 adults with limited literacy. Participants correctly answered an average of 59% of comprehension questions. The percentage of respondents correctly answering individual comprehension questions ranged from 26% to 92%. A multivariate analysis suggested that type of information (risk vs. other) and channel (text vs. audio) predicted comprehension. There was a significant interaction effect for literacy and place of birth. Our results suggest key areas for future research on comprehension of DTC advertising.