This dissertation 1) described prevalence and correlates of poly-tobacco use among US youth and young adults; 2) addressed positive and negative transitions of e-cigarettes among US youth and adults and 3) examined the 2-year transition of dual e-cigarette/cigarette use among US adults in relation to nicotine dependence (ND) symptoms, interest in quitting, and cardiovascular disease (CVD) factors. Data from 2013-2016 of the Population Assessment of Tobacco and Health Study were used. In the first study, 3.6% of youth (12-17years) and 18.3% of young adults (18-34years) were current poly-tobacco users between 2013-2014. Common poly-tobacco products combination was cigarettes and e-cigarettes for youth and young adults. Among youth, heavy drinking was associated with higher odds of poly-tobacco use. Factors associated with higher odds of poly-tobacco use among young adults included males, younger adults (18-24years), those with lower levels of educational attainment, residing in the South, heavy drinking, and marijuana use. In the second study, between 2013-2016, e-cigarette use increased only in youth. Young e-cigarette users were more likely to be never cigarette smokers compared to older users. Among youth e-cigarette users at each wave, the proportion of never cigarette smokers rose from 24.1% in Wave 1 to 42.6% in Wave 3 (p=0.0001 for trends). Among adult e-cigarette dual users in Wave 1, 8.8% transitioned to no tobacco use at Wave 3, 6.2% to mono e-cigarette use, while 85% either relapsed to cigarettes (53.5%) or continued dual use (31.5%). In the final study, among 1,870 adult dual tobacco users from Wave 1, 25·8% (95% CI 23·5-28·3) remained dual users 2 years later, 11·9% (95% CI 10·5-13·5) reported no tobacco use (cessation transition), 7·0% (95% CI 5·5-8·7) reported e-cigarette mono use (harm reduction transition), and 55·3% (95% CI 52·6-58·0) reported cigarette mono use (relapse transition). In the adjusted regression analysis, ND severity was associated with lower odds of cessation (OR 0·36; 95% CI 0·15-0·88) and harm reduction (OR 0·18; 95% CI 0·04-0·82) transitions. Interest in quitting and CVD factors were not associated with cessation or harm reduction. Collectively, our study findings emphasize the need for stricter tobacco regulatory policies to prevent another tobacco epidemic