People use electronic cigarettes (e-cigarettes) for many reasons, but currently there are no comprehensive assessments of the motivations for tobacco vaping. The aim of the present study is to develop and test the initial construct validity of a new measure to assess reasons for e-cigarette use. We developed a 56-item measure based on the e-cigarette literature. This measure, along with demographic and tobacco use questions, was administered to adults who self-identified as past or present e-cigarette users on the Prolific crowdsourcing platform. The sample (n = 965) was randomly assigned into two analytic groups for exploratory factor analysis (EFA; n = 484) and confirmatory factor analysis (CFA; n = 481). The sample ranged from 19 to 77 (M = 36.6; SD = 11.5) years old, and 42.2% identified as women, 74.6% as White, 7.2% as African American, 4.7% as Asian/Pacific Islander, and 5.1% Hispanic/Latino. After removing highly correlated items and nonloading items on the EFA, the 56-item scale was reduced to 47 items across eight factors. The eight subscales assessing various motivation domains of e-cigarette use included social influence, alternative to cigarettes, pleasurable effects, harm reduction, dependence, cessation, weight/appetite, and smell/flavor domains. Cronbach’s α coefficients and preliminary analyses of differential motivation based on sex, age, and daily smoker status are presented. This study demonstrates the construct validity for the first comprehensive measure tested to assess reasons for e-cigarette use. This measure has potential to become a valuable assessment for researchers examining factors contributing to tobacco vaping among a variety of populations and settings.