Background: A model health district was initiated through a program of health system strengthening (HSS) in Ifanadiana District of southeastern Madagascar in 2014. We report population health indicators prior to initiation of the program. Methods: A representative household survey based on the Demographic Health Survey was conducted using a two-stage cluster sampling design in two strata-the initial program catchment area and the future catchment area. Chi-squared and t-tests were used to compare data by stratum, using appropriate sampling weights. Madagascar data for comparison were taken from a 2013 national study. Results: 1522 households were surveyed, representing 8310 individuals including 1635 women ages 15-49, 1685 men ages 15-59 and 1251 children under age 5. Maternal mortality rates in the district are 1044/100,000. 81% of women's last childbirth deliveries were in the home; only 20% of deliveries were attended by a doctor or nurse/midwife (not different by stratum). 9.3% of women had their first birth by age 15, and 29.5% by age 18. Under-5 mortality rate is high: 145/1000 live births vs. 62/1000 nationally. 34.6% of children received all recommended vaccines by age 12 months (compared to 51.5% in Madagascar overall). In the 2 weeks prior to interview, approximately 28% of children under age 5 had acute respiratory infections of whom 34.7% were taken for care, and 14% of children had diarrhea of whom 56.6% were taken for care. Under-5 mortality, illness, care-seeking and vaccination rates were not significantly different between strata. Conclusions: Indicators of population health and health care-seeking reveal low use of the formal health system, which could benefit from HSS. Data from this survey and from a longitudinal follow-up study will be used to target needed interventions, to assess change in the district and the impact of HSS on individual households and the population of the district.