Although cigarette smoking during young adulthood is characterized by volatility, few studies examine if use of electronic nicotine delivery systems (ENDS) impacts transitions in cigarette use behaviors across this developmental period. The purpose of this longitudinal study was to examine the role of ENDS use on three transitions in cigarette smoking among young adults; initiation, desistance, and re-uptake. Methods: Participants were 5029 18–29-year-olds (64.2% female) enrolled in one of 24 Texas colleges at baseline and involved in an eight-wave, 4.5-year study. A multi-state, continuous time Markov model was used to assess the role of current/past 30-day and ever ENDS use on three transitions, spanning at least six months 1) never to current smoking (initiation); 2) current to non-current smoking (desistance); and 3) non-current to current smoking (re-uptake). The model also contained time-invariant socio-demographic, and time-varying intrapersonal (other tobacco use, nicotine dependence, sensation seeking, depressive symptoms) and interpersonal (peer cigarette use) covariates. Results: Both current and ever ENDS use increased the probability of transitioning from never to current cigarette use (initiation) and decreased the probability of transitioning from current to non-current use (desistance). Current, but not ever, ENDS use also increased the probability of transitioning from non-current to current use (re-uptake). Adjustment for socio-demographic, intrapersonal, and interpersonal covariates did not alter these findings. Discussion: ENDS use in young adulthood increases the risk for cigarette smoking behaviors across the continuum of uptake and progression. Prevention and cessation efforts targeting both ENDS and cigarette use during young adulthood are needed. •There were numerous cigarette transitions, but stable never use was most prevalent.•The role of ENDS in cigarette use transitions across young adulthood is not known.•ENDS use elevated risk of smoking initiation and decreased probability of desistance.•ENDS use elevated risk for the re-uptake of smoking after a period of non-use.