Epilepsy is a common neurological disorder, with potentially devastating consequences, and thus, elucidating the etiology bears immense potential for developing methods for early detection and prevention, targeted treatment options, and overall improvements to quality of life for millions of people worldwide. In 2007, the Epilepsy Phenome/Genome Project (EPGP) set out to compile the largest ever, detailed phenotype-genotype dataset to begin to unravel the complex genetic underpinnings of epilepsy. Over the course of five years, the EPGP sought to enroll a total of 5,250 participants consisting of two cohorts: 1,500 pairs of first-degree relatives with idiopathic generalized epilepsy or localization related epilepsy and 750 triads, or individuals diagnosed with Infantile Spasms, Lennox-Gastaut Syndrome, or certain malformations of cortical development and their unaffected, biological parents. Enrolling an adequate number of eligible research participants is paramount to any study involving human subjects. Despite this, barriers to participant recruitment and accrual persist in a majority of trials, and literature pertaining to methods for overcoming such challenges remains scarce. Like most clinical trials, the EPGP encountered obstacles to participant accrual, and by the end of its first year, net participant enrollment was only 52% of the projected target for that time. To ameliorate this, the EPGP's central administrative team set in motion a multifaceted, dynamic participant recruitment campaign to bolster outreach and increase enrollment numbers. A systematic, retrospective review of the various participant recruitment methods and their respective outcomes was performed. Data was compiled from the EPGP's reporting server, central recruitment database, and other relevant reports and files compiled by the EPGP's administrative team. The various methods implemented by the EPGP to boost participant enrollment include hiring a full-time recruitment director, implementing a National Participant Recruitment Campaign and centralized eligibility pre-screening process, revising the protocol and eligibility criteria, and nearly doubling the size of the network of clinical centers. The centralized screening process facilitated a mechanism for tracking the amount of traffic each recruitment method generated, and this information was analyzed retrospectively. The most successful recruitment methods were found to be those that involved partnerships with healthcare providers and community organizations who have direct and widespread access to the EPGP's target patient population. Less effective methods, in terms of percent of contacts meeting eligibility criteria, were those that did not specifically target people with epilepsy but rather reached a larger demographic. In total, more than 2,000 individuals or families contacted the EPGP centrally, 80% of those underwent eligibility pre-screening with 242 units (579 participants) enrolled in the EPGP as of February 2014. This accounts for 14% of enrollment study-wide, which is analogous to the individual contributions of the EPGP' top enrolling clinical centers. Beyond the recruitment strategies and methods implemented by the campaign, revisions to the EPGP's protocol, modifications to the eligibility criteria, and network expansion resulted in an increase in participant accrual. The number of clinical centers involved in the EPGP was found to positively correlate with participant accrual. Ultimately, a total of 5,442 participants, or 104% of the total enrollment target, were consented to participate. Of those, 4,099 participants, or 78% of the total enrollment target, remain enrolled as of February 28, 2014. The EPGP enrolled more than 75% of target for five of the seven participant types and managed to enroll no less than 50% of target for all participant types. While the results reported are limited by an analysis of the resources required to initiate and carry out the various recruitment methods, the lessons learned during the course of the EPGP may serve to benefit other multi-institutional trials with similar considerations in their recruitment planning. The EPGP's approach to boosting participant accrual was not only successful but also essential to paving the way towards identifying the complex genetic causes and phenotypic manifestations of idiopathic epilepsy syndromes.