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Hispanic/Latinx youth are at increased risk of electronic (e)-cigarette use (Wang et al, 2019). Early initiation of e-cigarette use is linked to later substance use (SU) disorders (Stone et al., 2012); thus, identifying factors impacting initiation is of high significance. Parenting practices reflecting warmth (e.g., relationship quality) and control (e.g., parental monitoring), as well as SU-specific practices (i.e., reactions to use), are known to mitigate adolescent SU (Yap et al., 2017). Moreover, tensions arising from intergenerational acculturative differences are linked to greater levels of adolescent SU (Martinez et al., 2017). Accordingly, it is imperative to examine how cultural experiences (e.g., acculturative stress) may reduce the effectiveness of protective parenting mechanisms and compound the risk of e-cigarette use within vulnerable populations. Using moderated mediation, this study examined whether acculturative gap conflicts moderate the association between relationship quality and parental monitoring on e-cigarette use specific parenting practices, and whether e-cigarette use specific parenting practices mediate the association between relationship quality and parental monitoring to subsequent e-cigarette use. Mediation was expected among families endorsing low acculturative gap conflicts. Participants enrolled in a larger NIH-funded longitudinal study that reported a cultural identity other than American were assessed (N = 123). Adolescents (Mage = 14.95 years, SD = 0.69; 65.0% female) and their caregivers (Mage = 44.82, SD = 5.76; 91.1% female) were predominantly White (89.4% and 91.1%) and Hispanic/Latinx (90.2% and 91.9%). At Time 1, adolescents completed the Parental Monitoring Instrument (Stattin & Kerr, 2000), assessing parental monitoring and relationship quality. At Time 2, dyads completed the Parental Attitudes and Reactions to Substance Use (PAR) Scale (Kodl & Mermelstein, 2004), assessing (1) adolescent-perceived caregiver reactions to e-cigarette use, and (2) caregiver-perceived e-cigarette parenting self-efficacy. At Time 2, adolescents completed the Acculturation Gap Conflict Inventory (Basanez et al., 2014) and reported e-cigarette use since the last visit. Two moderated multiple mediator regression models (i.e., relationship quality and parental monitoring) were estimated, controlling for adolescent age, sex, ethnicity, and adolescent and caregiver lifetime e-cigarette use at Time 1. Acculturative gap conflict significantly moderated the association between relationship quality and e-cigarette parenting self-efficacy (p = 0.02), such that at low (p < 0.001) and mean (p = .003), but not high (p = 0.86) levels of acculturative gap conflict, better relationship quality led to higher parenting self-efficacy. Moreover, there was a significant moderated mediation effect through e-cigarette parenting self-efficacy (effect = 0.12, 95% CI [0.01, 0.31]). Among adolescents who reported low (effect = -0.30, 95% CI [-0.70, -0.04]) and mean (effect = -0.18, 95% CI [-0.43, -0.02]) levels of acculturative gap conflict, e-cigarette parenting self-efficacy mediated the association between relationship quality and e-cigarette use. There was no evidence of moderation or mediation in the parental monitoring model. Despite prior work supporting the stronger role of parental monitoring in reducing adolescent SU, these outcomes suggest that relationship quality may have a more profound impact on e-cigarette use via a caregiver’s belief that they can prevent their child from using substances, especially among families sharing similar attitudes towards acculturation.