Youth and young adults (YYAs) are vulnerable populations for e-cigarette use or vaping. This study examined the effect of YYAs’ health information seeking behavior (HISB) around e-cigarette use and vaping on their subsequent vaping behavior. We conducted a nationally representative longitudinal phone survey of 13–25 year olds from June 2014 to September 2016, with 2,413 respondents who completed a baseline and follow-up survey six months later. The results from lagged logistic regressions and mediation analyses showed a) that information seeking predicted higher likelihood of vaping six months later even after controlling for baseline smoking and vaping status, intention to vape, and demographics, and b) that information seeking partially mediated the relationship between intention to vape and subsequent vaping behavior. Theoretical and regulatory implications are discussed.