Objectives: The two-fold purpose of this analysis is first to contrast the maternal risk factors and birth outcomes of American Indians (AIs) with other race/ethnic groups and to compare the maternal risk factors and birth outcomes of AIs by region to assess whether there are geographic variations in the adverse outcomes that might suggest intervention strategies. Study Design: This study used the National Center for Health Statistics live birth infant death cohort files from 1995-2001. Singleton live births to U.S. resident mothers were selected. The analyses were limited to non-Hispanic American Indians, including Aleuts and Eskimos (n = 239,494), Non-Hispanic White (n = 5,488,133), and Hispanic births (n = 5,284,978). Results: This comparison of birth characteristics and outcomes by ethnic group revealed that AIs have more adverse maternal risk factors (e.g., unmarried and <18 years of age) than Whites and Hispanics. After adjustment for these factors, AIs have higher risks of low birth weight and preterm birth and elevated risks of postneonatal and infant mortality. Their cause-specific rates for perinatal, SIDS, injury and infection are also higher. The regional analysis indicated the South/ Northeast have more low birth weight and preterm problems, but the Mid-West has the highest risks of infant mortality among LBW infants gestational age-specific mortality rates, and mortality from SIDS. Conclusions: These data show that AIs are not a homogenous group as evinced by distinct regional differences. SIDS is mainly a problem in the Mid-West, suggesting the involvement of environmental factors in that region. Further investigation is needed to examine the current AI perinatal health concerns. © Springer Science+Business Media, LLC 2007.