Introduction: Cigarette package inserts that describe quitting benefits and tips may promote cessation; however, research is needed to understand better their effects, including potentially enhancing the effects of pictorial health warning labels (PHWLs)., Methods: A randomized trial with a 2×2 factorial design was conducted with adult smokers (n=356) assigned to either small text-only health warning labels (HWLs; control); inserts with cessation messages, and the small text-only HWLs (inserts-only); large PHWLs (PHWLs-only); both inserts and PHWLs (inserts + PHWLs). Participants received a 14-day supply of their preferred cigarettes with packs labeled to reflect their group. Upon finishing the trial, participants reported their past 14-day frequency of noticing, reading, thinking about smoking harms and cessation benefits, talking about labels, and forgoing cigarettes because of the labels. Ordered logistic models regressed these outcomes on labeling groups, and mediation analyses assessed whether attention (i.e. noticing, reading) to labels mediated effects of labeling exposure on other outcomes (i.e. thinking about harms/benefits, talking, forgoing)., Results: The inserts + PHWLs group reported higher frequencies than the control group for all outcomes. Compared to the control group, both the inserts-only and PHWLs-only groups reported higher frequency of noticing (AOR=3.53 and 2.46, respectively) and reading labels (AOR=2.89 and 1.71), thinking about smoking risks because of the labels (AOR=1.93 and 1.82), and talking about labels (AOR=2.30 and 2.70). Participants in the inserts-only group also reported more frequent thinking about quitting benefits (AOR=1.98). Attention mediated all labeling effects except for the contrast between PHWLs only and control., Conclusions: Compared to text-only HWLS, cigarette labeling that involves inserts, PHWLs, or both appears more effective at drawing attention to warnings, which mediated the effects on cessation-related psychosocial and behavioral outcomes., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. All the authors report that since the initial planning of the work, this study was supported by the National Cancer Institute of the National Institutes of Health. J.W. Hardin reports that in the past 36 months participated on scientific review board of Celgene (Bristol Myers Squibb), which is unrelated to this manuscript. E.E. Hackworth reports that in the past 36 months received support for attending meetings and travelling from the National Institute on Drug Abuse, Society for the Study of Addiction, University of South Carolina. J.F. Thrasher reports that in the past 36 months there were grants or contracts from the UK Medical Research Council, the University of South Carolina, the Food & Drug Administration/NIH, the Canadian Institutes of Health Research, the Australian National Health and Medical Research Council and the American Cancer Society. In the past 36 months, he has also received consulting fees from the University of Stirling and has received payments for lectures/ presentations from the University of Alabama. He has also participated on the University of South Carolina Board for NIH for a funded clinical trial. Finally, J.F. Thrasher reports that in the past 36 months participated in the “Smokefree South Carolina” and the Tobacco Product Scientific Advisory Committee of the US Food and Drug Administration. J. Niederdeppe reports that in the past 36 months there were grants or contracts from the Agency for Research on Healthcare Quality (Grant to Cornell), Robert Wood Johnson Foundation (Multiple Grants to Cornell), National Institute of Diabetes and Digestive and Kidney Diseases (Grant to Cornell) and the National Science Foundation (Grant to Cornell). In the past 36 months, he has also received Payment for service on academic panel during Policy Dissemination Science workshop from New York University, Honorarium for public lecture and keynote speech + travel reimbursement from Peking University, a small payment (which is standard) for service on several grant review panels from NIH Office of the Director. He also reports that he has travelled for several workshops and consensus committee report meetings paid for by the National Academies (no honoraria or consulting fee is part of this work) from the National Academy of Medicine, and has travelled to Monterrey for a 2-day meeting to inform public health investments for the Hayward Institute (received small honorarium as well) from the Hayward Institute. In the past 36 months, he has offered service on center grant EAB, including consulting payment and travel to one meeting/year from the University of North Carolina, and has offered service on center grant EAB, including consulting payment and travel to one meeting/year from the University of Wake Forest. Finally, J. Niederdeppe reports that in the past 36 months he had an unpaid role on BOD for local non-profit that provides mental health and wellness services from Family & Childrens Service of Ithaca. M. Kim reports that in the past 36 months there were grants or contracts from the National Institute of Drug Abuse and the Food and Drug Administration., (© 2024 Lambert V.C. et al.)