Underage drinking and drug use in the Unites States (U.S.) constitute major public health concerns (National Institute on Alcohol Abuse and Alcoholism [NIAAA], 2010; National Institute on Drug Abuse [NIDA], 2009). Underage drinking and drug use are associated with a myriad of significant developmental, social, behavioral and health problems (Komro & Toomey 2002; Spoth, Greenberg, & Turrisi, 2008). Although alcohol use and dangerous patterns of drinking and drug use are widespread among all adolescents in the U.S., Hispanic adolescents are disproportionately affected by both alcohol and drug use. For example, findings from the Monitoring the Future study reveal that Hispanic 8th and 10th graders’ use of both alcohol and drugs (with the exception of amphetamines) was higher than both non-Hispanic white and Black 8th and 10th graders, respectively (Johnston et al., 2010). This is particularly alarming for two reasons: 1) Hispanics constitute the largest and fastest growing ethnic group in the U.S. and are a youthful population with 39% under 19 years old (Marotta & Garcia, 2003), and 2) research has indicated that the early onset of alcohol and drug use is strongly associated with future abuse and dependence (Amaro & Cortes, 2003; NIAAA, 2010). In spite of this, few culturally-specific interventions have been found to be efficacious in preventing and reducing alcohol and drug use among Hispanic adolescents (Szapocznik, Prado, Burlew, Williams, & Santisteban, 2007). One intervention is Familias Unidas (Prado et al., 2007; Pantin et al., 2009). Familias Unidas is a Hispanic-specific, family-based, substance use (including alcohol and drugs) preventive intervention (Pantin et al., 2009; Prado et al., 2007). Familias Unidas is guided by ecodevelopmental theory (Szapocznik & Coatsworth, 1999) and informed by culturally specific models developed for Hispanic populations in the U.S. (Szapocznik & Kurtines, 1993; Szapocznik & Williams, 2000). Consistent with Hispanic cultural values, Familias Unidas places parents in positions of leadership and expertise in helping to prevent alcohol and drug use in youth by increasing positive parenting, family support of the adolescent, parental involvement, general parent-adolescent communication and parent-adolescent communication regarding substance use (Pantin, et al., 2004). Furthermore, Hispanic youth tend to acculturate faster as compared to their parents, and thereby creates stressors within the family, which in turn might affect family functioning. Thus, Familias Unidas aims to increase parental knowledge with respect to U.S. cultural norms, which in turn might help ameliorate family functioning, including improved parent-adolescent communication with regard to differences in cultural perspectives (Prado & Pantin, 2011). Familias Unidas has demonstrated overall efficacy in preventing and reducing alcohol and drug use among Hispanic youth (Pantin et al., 2009; Prado et al., 2007). However, although little is known with respect to the efficacy of family-based interventions to prevent/reduce alcohol and drug use among Hispanic adolescents, even less is known with regard to which interventions are efficacious with which Hispanic subgroups (Castro et al., 2006). Thus, to tailor interventions aimed to maximize efficacy in Hispanic populations, there remains the need to examine moderating factors such as nativity status, which has been shown to moderate intervention effects in other interventions (Martinez & Eddy, 2005). Therefore, the purpose of this study was to investigate whether the effects of Familias Unidas (Prado et al., 2007; Prado & Pantin, 2011), as compared to community practice, on Hispanic adolescent alcohol and drug use varies by nativity status (i.e., U.S.-born and foreign-born). Acculturation is a bi-dimensional process whereby the attitudes and/or behaviors of people from their culture of origin are modified as a result of contact with the host culture (Berry, 2003). Research examining the effects of acculturation on alcohol and drug use among Hispanics in the U.S. has shown mixed findings (Lara, Gamboa, Kahramanian, Morales, & Bautista, 2005). Whereas some research has demonstrated that higher levels of acculturation are associated with increased risk of alcohol and drug use (Caetano, Ramisetty-Mikler, Rodriguez, 2009; Vega & Gil, 1998), other studies show no effects (e.g., Epstein, Doyle, & Botvin, 2003). The difference in findings has been partly attributed to the fact that different proxies have been used to measure acculturation (Lara et al., 2005). Although a number of proxies have been used to measure acculturation in Hispanic populations (Lara et al., 2005), nativity status in particular has been utilized in alcohol and drug research (Caetano et al., 2009; Vega & Gil, 1998). Thus, nativity status is not acculturation in and of itself, but rather one proxy by which acculturation is generally operationalized (Lopez-Class, Castro, & Ramirez, 2011; Schwartz, Unger, Zamboanga, & Szapocznik, 2010). Nativity status as a proxy of acculturation assumes that the acculturation phenomenon can be estimated by the amount of exposure one has to the mainstream culture (Lara et al., 2005). In fact, nativity status has been identified as one potential important proxy of acculturation by which differential effects of prevention interventions occur among Hispanic youth (Martinez & Eddy, 2005). For example, in a study evaluating a family intervention, Martinez and Eddy (2005) found stronger intervention effects on depression for U.S.-born Hispanic adolescents, relative to foreign-born participants. The current study was a secondary analysis on the efficacy of Familias Unidas in preventing/reducing alcohol and drug use in Hispanic adolescents (Pantin et al., 2009). Specifically, the primary goal of this study was to examine whether the effects of Familias Unidas, as compared to community practice, on Hispanic adolescent alcohol and drug use varies by nativity status (i.e., U.S.-born and foreign-born). Because previous research has shown stronger intervention effects for relatively higher family risk groups (Pantin et al., 2009; Prado & Pantin, 2011; Prado et al., 2007) and U.S.-born adolescents on other outcomes (Martinez & Eddy, 2005), we expect that, relative to community practice, Familias Unidas will be more efficacious at reducing/preventing both alcohol and drug use for U.S.-born adolescents.