OBJECTIVES:  To demonstrate the potential value of electronic health records (EHR) from an integrated healthcare system in the USA to enroll research subjects by simulating the inclusion/exclusion criteria of an ongoing cardiovascular (CV) outcomes trial with high dose eicosapentaenoic acid (EPA), a prescription omega-3 fatty acid. METHODS:  Reduction of Cardiovascular Events with EPA - Intervention Trial (REDUCE-IT) is a Phase III trial evaluating the safety and efficacy of 4 grams daily of high dose EPA (Vascepa®) in reducing first major CV events in a high-risk patient population. Enrolled adults have LDLc levels 40-100 mg/dL on statin therapy and high triglyceride (TG) levels (150-499 mg/dL). Inclusion criteria included established atherosclerotic CV disease (ASCVD) (risk group 1; RG1) and treated diabetes plus one or more ASCVD risk factors (risk group 2; RG2). We used the comprehensive EHR from the Northwest and Southern California regions of Kaiser Permanente to identify patients who met inclusion criteria for RG1 and RG2.. We applied exclusion criteria from REDUCE-IT (heart failure, malignant cancer, surgery, and liver, kidney, or thyroid function abnormalities) to better identify a target population. RESULTS:  Of 25,432 subjects who met inclusion criteria, 12,097 were assigned to RG1 and 13,335 to RG2. A total of 57.8% (n=6,996 ) and 45.2% (n=6,030) in RG1 and RG2 met at least one exclusion criterion. The most common exclusion criteria for RG1 included: heart failure (28%), cancer (25%), and planned surgery (15%); and for RG2: low renal function (16%) and cancer (15%). CONCLUSIONS: Our results demonstrate that EHRs from large integrated healthcare systems may be an efficient tool to screen and enroll populations of interest in a CV outcome trial. Pre-screening with EHR data has the potential for substantive reductions in clinical trial recruitment time and cost by pre-excluding subjects that will not qualify.