A systematic method was used to review the existing epidemiologic literature and determine the state of the scientific evidence for potential adverse health outcomes in populations living near oil and natural gas (ONG) operations in the United States. The review utilized adapted systematic review frameworks from the medical and environmental health fields, such as Grading of Recommendations, Assessment, Development and Evaluations (GRADE), the Navigation Guide, and guidance from the National Toxicology Program’s Office of Health Assessment and Translation (OHAT). The review included 20 epidemiologic studies, with 32 different health outcomes. Studies of populations living near ONG operations provide limited evidence (modest scientific findings that support the outcome, but with significant limitations) of harmful health effects including asthma exacerbations and various self-reported symptoms. Study quality has improved over time and the highest rated studies within this assessment have primarily focused on birth outcomes. Additional high-quality studies are needed to confirm or dispute these correlations.