Introduction:Electronic health records (EHRs) have the potential to offer real-time, inexpensive standardized health data about chronic health conditions. Despite rapid expansion, EHR data evaluations for chronic disease surveillance have been limited. We present design and methods for the New York City (NYC) Macroscope, an EHR-based chronic disease surveillance system.This methods report is the first in a three part series describing the development and validation of the NYC Macroscope. This report describes in detail the infrastructure underlying the NYC Macroscope; indicator definitions; design decisions that were made to maximize data quality; characteristics of the population sampled; completeness of data collected; and lessons learned from doing this work. The second report describes the methods used to evaluate the validity and robustness of NYC Macroscope prevalence estimates; presents validation results for estimates of obesity, smoking, depression and influenza vaccination; and discusses the implications of our findings for NYC and for other jurisdictions embarking on similar work. The third report applies the same validation methods to metabolic outcomes, including the prevalence, treatment and control of diabetes, hypertension and hyperlipidemia.Methods:We designed the NYC Macroscope for comparison to a local “gold standard,” the 2013–14 NYC Health and Nutrition Examination Survey, and the telephonic 2013 Community Health Survey. NYC Macroscope indicators covered prevalence, treatment, and control of diabetes, hypertension, and hyperlipidemia; and prevalence of influenza vaccination, obesity, depression and smoking. Indicators were stratified by age, sex, and neighborhood poverty, and weighted to the in-care NYC population and limited to primary care patients. Indicator queries were distributed to a virtual network of primary care practices; 392 practices and 716,076 adult patients were retained in the final sample.Findings:The NYC Macroscope covered 10% of primary care providers and 15% of all adult patients in NYC in 2013 (8–47% of patients by neighborhood). Data completeness varied by domain from 98% for blood pressure among patients with hypertension to 33% for depression screening.Discussion:Design and validation efforts undertaken by NYC are described here to provide one potential blueprint for leveraging EHRs for population health monitoring. To replicate a model like NYC Macroscope, jurisdictions should establish buy-in; build informatics capacity; use standard, simple case defnitions; establish documentation quality thresholds; restrict to primary care providers; and weight the sample to a target population.