© 2017 Elsevier B.V. Background and aims With no established standard for assessing tobacco dependence (TD) across tobacco products in surveys, the Population Assessment of Tobacco and Health (PATH) Study provides a unique platform for examining the psychometric properties and validity of multiple indicators of tobacco dependence across a range of tobacco products. Participants A U.S. nationally representative sample from the 32,320 adult Wave 1 interviews with analyses focused on 14,287 respondents who were current established users of tobacco products. Findings This analysis confirms a single primary latent construct underlying responses to TD indicators for cigarettes, e-cigarettes, cigars, hookah, and smokeless tobacco products. Mutually exclusive past year tobacco-user groups included: cigarette only (n = 8689), e-cigarette only (n = 437), cigar only (traditional, cigarillo, or filtered) (n = 706), hookah only (n = 461), smokeless tobacco only (n = 971), cigarette plus e-cigarette (n = 709), and multiple tobacco product users (n = 2314). Differential Item Functioning (DIF) analyses supported use of 16 of the 24 examined TD indicators for comparisons across tobacco users. With cigarette users as a reference (mean = 0.0, SD = 1.0), we observed a range of TD with hookah (mean = −1.71) and cigar (mean = −1.92) only users being the lowest, and cigarette plus e-cigarette product users being the highest (mean = 0.35). Regression models including sociodemographic factors supported concurrent validity with increased product use frequency and TD among cigarette-only (p < 0.001), e-cigarette only (p < 0.002), cigar (p < 0.001), hookah only (p < 0.001), and smokeless tobacco users (p < 0.001). Conclusion The PATH Study Adult Wave 1 Questionnaire provided psychometrically valid measures of TD that enables future regulatory investigations of nicotine dependence across tobacco products.