Endorsing prototypes of cigarette smokers predicts cigarette smoking, but less is known about prototypes of users of other tobacco products. Our study sought to establish the reliability and validity of a measure of prototypes of smokers and e-cigarette users. Participants were from a national survey of smokers and non-smokers (n = 1414), a randomized clinical trial (RCT) of adult smokers (n = 2149), and adolescent children of adults in the trial (n = 112). The Prototypes of Tobacco Users Scale (POTUS) has four positive adjectives (cool, sexy, smart, and healthy) and four negative adjectives (disgusting, unattractive, immature, and inconsiderate) describing cigarette smokers and e-cigarette users. Confirmatory factor analyses identified a two-factor solution. The POTUS demonstrated strong internal consistency reliability in all three samples (median α = 0.85) and good test–retest reliability among adults in the RCT (median r = 0.61, 1–4 weeks follow-up). In the RCT, smokers more often agreed with negative prototypes for smokers than for e-cigarette users (mean = 2.03 vs. 1.67, p < 0.05); negative prototypes at baseline were also associated with more forgoing of cigarettes and making a quit attempt at the end of the trial (Week 4 follow-up). The POTUS may be useful to public health researchers seeking to design interventions that reduce tobacco initiation or cessation through the manipulation of tobacco user prototypes