Electronic Health Records (EHRs) are widely recognized for their potential to revolutionize healthcare and health research. Little has been published about the transformative ways in which EHRs can be used to optimize the performance of clinical trials. EHR systems can be valuable tools for assessing potential trial populations, recruiting patients, and enhancing trial efficiency, cost-effectiveness, quality, and accuracy. Geisinger Health System has been using an EHR since the late 1990s. All care delivered at Geisinger-inpatient and outpatient care at any Geisinger hospital or community practice site-is recorded within the EHR. We review the use of EHRs to recruit for 5 large randomized clinical trials at Geisinger, reporting the power and pitfalls associated with its use. The utilization of the EHR can transform how clinical trials are performed, but changes within the industry will be needed to fully realize the benefits.