Introduction: Constances is a very large, general-purpose population-based cohort designed for health research and to provide information for public health purposes. Materials and Methods: The cohort consists of a sample intended to be representative of the French population aged 18 to 69; the planned total sample size is 200,000 participants. Participants are enrolled at Social Security Health Examination Centers (CES), where they undergo a medical examination and complete a questionnaire regarding their health, lifestyle, and employment history. A biobank (blood and urine) is established. Follow-up is conducted via an annual self-administered questionnaire, a medical examination every five years, and by linking data to the databases of Sniiram (National Inter-Regime Health Insurance Information System), Cnav (National Old-Age Insurance Fund), and CépiDc-Inserm (Center for Epidemiology on Medical Causes of Death). The data collected from these various sources pertain to health, socio-professional characteristics, healthcare utilization, and biological, physiological, physical, and cognitive parameters. Quality control and validation of health events have been implemented. Selection bias is accounted for using a random sample of non-participants. Status: Currently (October 2016), more than 115,000 participants have been included in the cohort, and approximately 3,000 new volunteers are enrolled each month. More than 60 projects covering a wide range of topics have been approved by the cohort’s International Scientific Advisory Board. Public-private partnerships have also been established, as provided for under the funding of Constances by the Investments for the Future program.