Background: The Public Health Alliance of Southern California, a coalition of 9 local health departments, developed a metric - the Health Disadvantage Index (HDI) - to rank California census tracts by cumulative health disadvantage based on social determinants of health. The goal was to create a place-based tool with fine geographic resolution to guide local and state priority setting. It also served as an alternative to CalEnviroScreen (CES), California EPA's pollution-oriented index, which prioritized 25% of census tracts for pollution enforcement and environmental justice funding. Methods: Twenty-seven indicators were organized into economic, social, educational, neighborhood, health, and environmental domains consistent with a literature review. Indicators were measures of prevalence selected from publically available statewide sources, including the American Community Survey, 2008-2012. Z-scores were calculated for each indicator and were averaged within domains. The overall HDI score summed domain scores using weights informed by literature reviews. We defined disadvantaged communities as census tracts in the highest quartile of HDI and CalEnviroScreen. We cross-classified census tracts of HDI and CES in 4-fold tables to assess concordance and mapped the geographical distribution (http://phasocal.org/ca-hdi/). Local health departments ground-truthed the findings based on knowledge of their communities. Results: HDI and CES were concordant in 1329 census tracts (6 million people). In the 630 discordant, most disadvantaged HDI tracts (2.8 million), poverty and other indicators in the social, economic, education, and health domains were significantly worse than in the 637 discordant, most disadvantaged CES tracts (3 million). In discordant tracts, pollution burden was higher for CES than HDI. HDI identified more rural census tracts as disadvantaged than CES. Based on recommendations from a steering committee of local health departments, the HDI was refined by using statistical methods to derive domain weights that produced an HDI score with a high correlation to life expectancy at birth. The results were presented to public health departments and other policymakers along with key messages and talking points. Conclusion: Indices using different conceptual frameworks led to large differences in the populations considered disadvantaged. Tools to classify cumulative disadvantage should align their framing with their purpose.