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Multipayer initiatives have sought to address social determinants of health, such as food insecurity, by linking primary care patients to social services. It remains unclear whether such social determinants contribute to avoidable short-term health care costs.We sought to quantify costs and mitigating factors for the increased risk of hypoglycemia at the end of each month among low-income Americans, a phenomenon related to exhaustion of food budgets.We used claims data on 595,770 commercially insured American adults aged 19 through 64 years old from 2004 through 2015 to estimate the risks and costs of emergency room visits and inpatient hospitalizations for hypoglycemia during the last week of each month versus prior weeks.Although persons with household incomes greater than the national median did not experience a monthly cycle of hypoglycemia, those with incomes less than the national median had an odds ratio of 1.07 (95% confidence interval, 1.02–1.12; P=0.005) for emergency room visits or inpatient hospitalizations for hypoglycemia during the last week of each month, compared with earlier weeks. The risk of end-of-the-month hypoglycemia was mitigated to statistical insignificance during a period of increased federal nutrition program benefits from 2009 through 2013. Eliminating the monthly cycle of hypoglycemia among commercially insured nonelderly adults would be expected to avert $54.1 million per year (95% confidence interval, $0.8–$204.0) in emergency department and inpatient hospitalization costs.Addressing the end-of-the-month increase in hypoglycemia risk among lower-income populations may avert substantial costs from emergency department visits and inpatient hospitalizations.