BACKGROUND: Using a theoretically-grounded approach to the epidemiological study of HIV incidence among a national, diverse sample of sexual and gender minority (SGM) men (age 17 -29 years), as well as examining HIV incidence through an innovative geospatial lens, is of considerable public health significance. Our overarching objectives are to assemble a U.S.-based national cohort of diverse SGM men: (1) to estimate HIV incidence in SGM men followed every 6 months for up to 24 months, (2) to assess the association of individual and geospatial factors associated with HIV incidence and (3) to determine the relative efficiency and acceptability of three different, discrete study enrollment approaches (including completion of remote HIV testing). The purpose of this manuscript is to describe the study protocol. METHODS: The cohort is composed of English- and/or Spanish-speaking SGM men at risk for HIV, age 17-29 years and living in the United States and its territories. We used multiple methods to recruit our sample including social networking apps like GrindrTM. If a participant was eligible for the study, they completed an address intake form so an HIV test could be mailed to their home or chosen address. We assembled three cohorts using different enrollment approaches. Cohort 1 used Zoom video calls with study staff observing participants use of OraQuick test with oral swabs at the baseline visit. Cohort 2 used No Zoom and OraSure oral fluid tests that participants mailed to an external lab. Cohort 3 used No Zoom/self-administration of OraQuick tests and participants uploading test results to an online portal (REDCap). DISCUSSION: This study will provide important data on multilevel determinants of HIV incidence among SGM men at the national level, allowing us to examine important differences by local jurisdiction, region and state and to better understand the impact of individual, social and geospatial factors on HIV incidence to help inform future prevention strategies.