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Introduction: Although Rwanda’s health system underwent major reforms and improvements after the 1994 Genocide, the health system and population health in the southeast lagged behind other areas. In 2005, Partners In Health and the Rwandan Ministry of Health began a health system strengthening intervention in this region. We evaluate potential impacts of the intervention on maternal and child health indicators. Methods: Combining results from the 2005 and 2010 Demographic and Health Surveys with those from a supplemental 2010 survey, we compared changes in health system output indicators and population health outcomes between 2005 and 2010 as reported by women living in the intervention area with those reported by the pooled population of women from all other rural areas of the country, controlling for potential confounding by economic and demographic variables. Results: Overall health system coverage improved similarly in the comparison groups between 2005 and 2010, with an indicator of composite coverage of child health interventions increasing from 57.9% to 75.0% in the intervention area and from 58.7% to 73.8% in the other rural areas. Under-five mortality declined by an annual rate of 12.8% in the intervention area, from 229.8 to 83.2 deaths per 1000 live births, and by 8.9% in other rural areas, from 157.7 to 75.8 deaths per 1000 live births. Improvements were most marked among the poorest households. Conclusion: We observed dramatic improvements in population health outcomes including under-five mortality between 2005 and 2010 in rural Rwanda generally and in the intervention area specifically.