Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Novel, technology-based methods are rapidly increasing in popularity across multiple facets of quantitative HIV research. Qualitative HIV research, however, has been slower to integrate technology into research methodology. One method, computer-mediated communication (CMC), has been utilized to a limited extent for focus group discussions. Objective: This study aimed to assess feasibility of an online video conferencing system to further adapt CMC to facilitate focus group discussions among transgender women living in six cities in eastern and southern U.S. Methods: Between August 2017 and January 2018, focus group discussions with adult transgender women were conducted in English and Spanish by research teams based in Boston, MA and Baltimore, MD. Participants were sampled from six cities: Baltimore, MD, Boston, MA, New York, NY, Washington, DC, Atlanta, GA, and Miami, FL. This was formative research to inform a technology enhanced cohort study to assess HIV acquisition among transgender women in these cities. This analysis focuses on the methodologic use of CMC focus groups conducted synchronously using online software that enables video or phone discussion. Findings are based on qualitative observations of attendance and study team debriefing on topics of individual, social, technical and logistical challenges encountered. Results: A total of 41 transgender women from all six cities participated in seven online focus group discussions (five English, two Spanish). An equal distribution of attendees were Black/African American and White race (34%), with 29% reporting Hispanic/Latina ethnicity. Overall, 29 of 70 eligible and scheduled transgender women failed to attend the focus group discussions. The most common reason for non-attendance was forgetting or having a scheduling conflict (55%); 14% reported technical challenges associated with accessing the CMC focus group discussion. CMC focus group discussions were found to facilitate geographic diversity; increase perceptions of anonymity and privacy (e.g., use of pseudonyms, option to use video); ease scheduling by eliminating challenges related to travel to a data collection site; offer flexibility to join via telephone (cell or landline), smart phone or tablet (through an application), or computer. Challenges encountered were overlapping conversations; variable audio quality in cases where Internet or cellular connection was poor; distribution of incentives (e.g., cash vs gift card). As with all focus group discussions, establishment of ground rules and employing a skilled facilitator were critical to the success of CMC focus group discussions. Conclusions: Synchronous CMC focus group discussions provide an efficient and secure opportunity to bring together transgender women across geographic space, without losing the standardized approach or reducing the quality that is expected of in-person focus group discussions. Participants with limited technological literacy, inconsistent access to a phone and/or cellular data/service, and circumstances necessitating immediate cash incentives may require additional support and accommodation when connecting to CMC focus group discussions.