Background and Objectives Research in the United States tends to indicate that immigrants from most sociogeographic regions have considerably lower substance use disorder (SUD) rates than native born individuals. We aimed to analyze the differences between immigrants and native born population regarding substance abuse and dependence. This objective was approached using data from the ARACAT cross-sectional multicenter study in primary care settings of two different Spanish regions: Aragon and Catalonia. Methods Three thousand six patients (1,503 immigrants randomly selected and 1,503 native born paired by age and gender) were interviewed using the Mini-International Neuropsychiatric Interview. Results Reported substance abuse and dependence were more prevalent in the native born population than in immigrants (alcohol abuse 5.1% vs. 2.6% p-<-.0001, alcohol dependence 3.3% vs. 2.6% n.s., other abuse 3.4% vs.4% p-<-.0001, other dependence.5% vs. 4.0% p-<-.0001). Large differences were detected between different ethnic groups. Sociodemographic characteristics such as female gender, older age, higher level of education or stable housing (among others), were found to be protective against different SUDs. Conclusions and Scientific Significance Immigrants have lower levels of alcohol and substance abuse, however, those that do consume show higher levels of both comorbid mental disorders and problematic alcohol/substance use. It would appear to be the case that issues specific to immigrant cultures, such as extreme stigmatization of substance and alcohol use, may serve to promote social marginalization and inhibit treatment access. (Am J Addict 2014;23:337-342) © American Academy of Addiction Psychiatry.