A malaria control program established in 2004 on Bioko Island, Equatorial Guinea, achieved significant reductions in malaria prevalence; however, progress subsequently stalled, leading to a proposal to develop and implement a highly effective malaria vaccine to increase impact. After conducting clinical trials of Sanaria® (Rockville, MD) Plasmodium falciparum (P. falciparum) sporozite vaccines against P. falciparum malaria, which demonstrated safety and efficacy, a larger phase 3 trial was planned to support vaccine licensure for specific target populations and eventual island-wide malaria elimination. The Equatorial Guinea Pilot Study for Recruitment, Screening and Participant Registry (EGRESPAR) assessed the health status of the target population and generated a registry of eligible children and adults. Households in areas with malaria prevalence ≥15% were randomly selected, aiming to register 2,100 healthy Equatoguineans divided equally into age groups of 1.5–9, 10–17, and 18–50 years. A total of 6,493 individuals from 1,807 households, who considered themselves or their children to be healthy, completed questionnaires; 2,021 were screened using phase 3 enrollment criteria, 643 were excluded, and 1,378 were entered into the registry. Among those screened, 13.6% had Plasmodium, 1.8% had Loa loa, 4.8% had hepatitis B, 0.5% had hepatitis C, and 2.1% had HIV. Adults were twice as likely to have clinically relevant medical conditions, such as obesity, hypertension, or diabetes, meeting exclusion criteria compared to children. In conclusion, there was a significant prevalence of infections and chronic medical conditions among Bioko Island residents who considered themselves or their children to be healthy and interested in clinical research participation, particularly in adults. The EGRESPAR successfully generated a registry to support the initiation of a large-scale phase 3 vaccine trial.