BACKGROUND: HIV infection rates among sexual minority men and transgender individuals, particularly adolescents and young adults, remain elevated in the United States despite continued improvement in the HIV public health response. However, there remains a knowledge gap in understanding the barriers faced by this community in receiving HIV care and prevention resources. To address this, the Keeping it LITE study was conducted to assess HIV risk factors and barriers to preventive treatment in a large national cohort of young sexual minority men and transgender individuals at high risk of HIV infection. OBJECTIVE: This study aims to evaluate the feasibility of enrolling a large remote cohort, challenges encountered in recruitment, and adjustments made to address these challenges. METHODS: A large national cohort (n=3444) of young sexual minority men and transgender individuals were recruited. Participants were recruited via advertisements on social media; social apps for lesbian, gay, bisexual, transgender, and queer individuals; print advertising; and word-of-mouth. Before enrolling, participants verified their HIV status using an at-home HIV test or by providing their own testing documentation. Descriptive statistics were generated, and a series of logistic regressions were conducted to evaluate demographic differences between recruitment methods, HIV testing methods, and enrollment status. RESULTS: The Keeping it LITE study was particularly successful in recruiting participants via social media, with over half of the participants recruited from advertisements on social media platforms such as Facebook, Instagram, and Snapchat. Participants were also recruited via word-of-mouth; lesbian, gay, bisexual, transgender, and queer apps (ie, Grindr, Scruff); and print advertisements, and participants recruited from these sources tended to be older and have a higher risk profile. The study was also successful in recruiting a large sample of transgender youth, particularly transgender men and nonbinary individuals. At-home HIV testing was acceptable and more heavily used by younger participants, although several barriers were encountered and overcome in the implementation of this testing. The study had more limited success in recruiting participants aged 13-17 years because of lower enrollment rates and barriers to advertising on social media platforms. The implications of these findings for the future development of HIV research and intervention protocols among sexual minorities and trans youth are discussed. CONCLUSIONS: The methods used in the Keeping it LITE study, particularly recruitment via social media, were found to be feasible and acceptable to participants.