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OBJECTIVE: Harm perceptions influence tobacco use decisions. People with substance use problems (PWSUPs) who also smoke cigarettes might have unique e-cigarette harm perceptions compared to the general population based on social (e.g., stigma) and personal factors that impact their worldview. The aims of this study are to examine, among adults who smoke: 1. the association between the harm perception of e-cigarettes relative to cigarettes and substance use problem severity, 2. whether changes in substance use problem severity over time are associated with changes in harm perceptions of e-cigarettes relative to cigarettes, 3. whether associations between harm perceptions and vaping initiation are moderated by SUP. METHODS: We used the nationally representative US Population Assessment of Tobacco and Health (PATH) Study Waves 1-7 dataset collected between 2013 and 2023. The study population comprised adults (18+) who smoked cigarettes in the past month. The primary predictor was substance use problem (SUP) severity (no/low, moderate, and severe). The outcome at follow-up were: 1. relative harm perception: “Is using e-cigarettes or other electronic nicotine products less harmful, about the same, or more harmful than smoking cigarettes,” 2. change in SUP status (from no/low at baseline wave to moderate or high severity at follow-up) and change in relative harm perceptions (from more/same harm at baseline to less harmful at follow-up), 3. nicotine vaping initiation.