Context-It is unknown whether rural isolation may affect birth outcomes and infant mortality differentially for Indigenous versus non-Indigenous populations. We assessed birth outcomes and infant mortality by the degree of rural isolation among First Nations (North American Indians) and non-First Nations populations in Manitoba, Canada, a setting with universal health insurance.Methods-A geocoding-based birth cohort study of 25,143 First Nations and 125,729 non-First Nations live births to Manitoban residents, 1991Manitoban residents, -2000. Degree of rural isolation was defined by an indicator of urban influence (no, weak, moderate/strong) based on the percentage of the workforce commuting to urban areas.Findings-Preterm birth and low birth weight rates were somewhat lower in all rural areas regardless of the degree of isolation as compared to urban areas for both First Nations and nonFirst Nations. Infant mortality rates were not significantly different across areas for First Nations (10.7, 9.9,7.9, and 9.7 per 1,000 in rural areas with no, weak, moderate/strong urban influence, and urban areas, respectively), but rates were significantly lower in less isolated areas for non-First For further information, contact: Zhong-Cheng Luo, PhD, Department of Obstetrics and Gynecology, Sainte-Justine Hospital, Bureau 4986, 3175, chemin Côte-Sainte-Catherine, Montreal, Quebec H3T 1C5, Canada; zhong-cheng.luo@recherche-ste-justine.qc.ca. Nations (7.4, 6.0, 5.6, and 4.6 per 1,000, respectively). Adjusted odds ratios showed similar patterns.Conclusions-Living in less isolated areas was associated with lower infant mortality only among non-First Nations. First Nations infants do not seem to have similarly benefited from the better health care facilities in urban centers, suggesting a need to improve urban First Nations' infant care in meeting the challenges of increasing urban migration.Keywords birth outcomes; infant mortality; North American Indians; rural and urban; rural isolation Birth outcomes are persistently worse among Aboriginal as compared to non-Aboriginal populations even in developed countries.-The underlying causes remain incompletely understood. Several studies indicate that the place of residence may affect the disparities in birth outcomes and infant mortality when comparing Aboriginal versus non-Aboriginal populations. Among North American Indians (the Canadian equivalent term "First Nations") and Alaskan Natives compared to whites in the United States, greater disparities in infant mortality have been reported in some urban areas than in rural areas., In British Columbia, the disparity in infant mortality when comparing First Nations to non-First Nations declined less substantially and less consistently in urban versus rural areas. A recent Australian study found that the disparity in infant mortality when comparing Aboriginal versus nonAboriginal populations was larger in remote rural areas. However, it is unknown whether the degree of rural isolation per se may affect birth outcomes and infan...