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 Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn.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: Voluntary medical male circumcision (VMMC) is a safe and effective HIV prevention strategy. However, adherence to recommended in-person, post-operative follow-up is inefficient for a procedure with few adverse events (AEs). Two-way text-based (2wT) follow-up appears as a safe and efficient alternative to scheduled clinic visits for low-risk patients. Objective: Within an ongoing randomized control trial of 2wT in South Africa, and complementary to human-centered design (HCD) processes of 2wT app optimization, we conducted a formative study focused on 2wT usability, exploring healthcare worker (HCW) thoughts, perceptions, and opinions on 2wT implementation in both urban and rural South Africa. Methods: We detail aspects of the 2wT HCD process. For usability and acceptability, seven healthcare workers (HCWs) using 2wT in Gauteng and the North West Province participated in key informant interviews. HCWs were asked their opinions on 2wT as a viable, useful, appropriate, and accessible method of post-operative MC care and workload reduction. The data was explored, coded, and analysed by three qualitative researchers using thematic content analysis and ATLAS.ti software. Results: Most HCWs felt confident, comfortable, satisfied, and well-supported using 2wT-based follow-up as an alternative to in-person clinical reviews. They felt the system was easy to use and required little technical support after initial system use mentoring. Few noted safety concerns for patients using 2wT as men were able to receive clinical guidance, reassurance, and referral via SMS. Although fewer in-person visits did reduce the workload and free up the clinical flow, HCWs did note the added burden of having to interact with clients via SMS on evenings or weekends as a drawback. Study workload was burdensome and understanding of research versus routine 2wT activities were unclear. For scale-up, HCWs reinforced the need for enhanced post-operative counselling on both 2wT responses and early signs of complications and suggested a rotation to spread the evening/weekend workload between nurses to ensure swift patient responses. Conclusions: In this formative qualitative study focused on HCWs, 2wT was strongly supported as an alternative to in-person post-operative reviews for MC patients in South Africa. HCD processes likely improved usability and acceptability of the 2wT app. HCWs supported scale-up of 2wT given the context of distance from the clinic to the men’s homes and the potential for reducing the HCW burden. For success, providers urged additional patient sensitization that 2wT augments, but not replaces, existing after-hours and emergency care services. Likewise, auxiliary MC workers are needed to respond outside of routine clinic hours, better fulfilling the workload reduction and quality care promises of 2wT.