Abstract While many countries require prominent pictorial health warning labels (PHWLs) on the outside of cigarette packs to communicate the harms of smoking, there is evidence that cigarette pack inserts that contain efficacy messages may enhance the effectiveness of PHWLs. The US Food and Drug Administration (FDA) has regulatory authority to communicate with smokers through inserts. While current labeling regulations do not require inclusion of inserts, the FDA could implement them in the future. This study assesses US smokers’ perceptions of cigarette package inserts at the conclusion of a two-week randomized trial on cigarette labeling where half of participants were exposed to insert messages (two response-efficacy messages and two self-efficacy messages) in their packs. Participants (n = 359) completed a 30- to 60-min interview with both quantitative and qualitative assessments, including measures of recall and perceived message effectiveness (PME) for specific inserts. Correlates of recall and PME were estimated using mixed-effects regression models. Qualitative responses to PME items were analyzed using thematic analysis. Response-efficacy messages had higher PME and recall than self-efficacy messages. People had diverse responses to the inserts, including that they were positive, thought-provoking, and helpful. Reactions to and perceptions of the inserts indicate potential benefits of integrating efficacy messages into labeling policies.