Background: Social media has become a popular method to recruit participants, particularly for studies with hard-to-reach populations. These studies still face challenges in data quality and, for longitudinal studies, sample retention. However, in addition to aiding in recruitment, social media platforms can help researchers with participant verification and tracking procedures during the study. There is limited previous research describing how longitudinal studies can use social media to screen and retain participants., Objective: This paper describes strategies implemented to screen and retain a nationwide sample of sexual minority youth who were recruited through social media platforms for a longitudinal study testing a drug abuse prevention program., Methods: Our screening strategies for participants included collecting necessary demographic information (name, phone, email, and social media accounts), verifying this information using publicly available web-based records, and sending confirmation emails to ensure working email addresses and correct dates of birth. Retention strategies included communications designed to develop positive participant relationships, incentives for survey completion, regular updating of participant contact information, targeting hard-to-reach participants, and using social media as an alternative means of contacting participants., Results: During enrollment, although the only demographic data required were a phone number and an email address, 87.58% (1065/1216) of participants provided their Instagram as an alternative means of contact. This form of alternative communication remains the most preferred with 87.40% (1047/1198) of participants continuing to provide an Instagram username as of January 2023, about 3 years after recruitment began. In comparison, other alternative means of contact (eg, Facebook and alternative email) were provided by only 6.43% (77/1198) to 56.18% (673/1198) of participants. Direct messaging on Instagram was used to successfully confirm participant identity, remind participants to take annual follow-up surveys, and update lost participant contact information. Screening and retention strategies used in the study have helped achieve 96.30% (1171/1216) to 96.79% (1177/1216) sample retention across 3 waves of data collection., Conclusions: Though social media can be a helpful tool to recruit participants, attrition and participant authenticity difficulties may be associated with this method. Screening and retention strategies can be implemented to improve retention. Internet searches are effective for screening youth to ensure they meet eligibility requirements. Additionally, social media-Instagram in this study-can help to track and locate participants who do not respond to traditional contact methods., Trial Registration: ClinicalTrials.gov NCT03954535; https://clinicaltrials.gov/study/NCT03954535., (©Margaret Weisblum, Emma Trussell, Traci Schwinn, Andrea R Pacheco, Paige Nurkin. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 28.02.2024.)