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Objective: Although substance use and problems among Mexican Americans are associated with both immigration to the United States and living at the U.S.-Mexico border, little is known about relationships between age at immigration and substance use by gender within the border context. The purpose of this study was to analyze the association of age at immigration with heavy alcohol use, alcohol use disorders (AUD), and drug use among Mexicans Americans living both on and off the U.S.-Mexico border.Method: Household surveys were conducted, using area probability sampling of 2,336 Mexican Americans (1,185 female), ages 18-65, living at the Texas-Mexico border in the metropolitan areas of Laredo and McAllen/Brownsville, and in the nonborder location of San Antonio.Results: Females immigrating before age 12 were less likely to report heavy alcohol use (odds ratio [OR] = 0.309), and those immigrating before age 21 were less likely to report any drug use during the last year compared with their U.S.-born counterparts (OR = 0.473; OR = 0.386, respectively). Males immigrating after age 20 were less likely to report heavy alcohol use (OR = 0.478), and those immigrating between ages 12 and 20 were less likely to report AUD (OR = 0.479) and drug use (OR = 0.255) compared with their U.S.-born counterparts. Early age at immigration (before age 12) was significantly associated with drug use for males living on the border compared with those living off the border.Conclusions: Findings suggest that among females, immigrating before age 12 (vs. being born in the United States) is protective against heavy alcohol and drug use, but among males, immigrating before age 12 results in similarly heavy patterns of use as their U.S.-born counterparts, partially supporting previous findings that early immigration is particularly risky in relation to substance use and AUD. [ABSTRACT FROM AUTHOR]