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Introduction Rapid antibody testing is a cornerstone in HIV case finding and management. Without tools for rapid detection and diagnosis of HIV infection, none of the downstream targets for linkage to antiretroviral therapy and viral suppression in the HIV treatment cascade could be achieved. In the Philippines, oral HIV self-testing (HIVST) has not been adapted for use. Moreover, no study has been conducted to determine HIV testing preferences and acceptability of oral HIVST among Filipino men who have sex with men (MSM) and transgender women (TGW). The protocol describes a mixed-method approach to evaluate HIV testing preferences and acceptability of oral HIVST vs currently available testing modalities among MSM and TGW in the Greater Manila Area and determine the factors underlying the participants’ selection of a testing modality.Methods and analysis This study will use an explanatory sequential mixed-methods design. The initial phase will involve a cross-sectional survey with a pre/post questionnaire format design targeting 480 MSM and 478 TGW. A case study phase follows, with 80 in-depth interviews to provide more detailed qualitative insights. Quantitative data will be analysed using multinomial logistic regression models, while qualitative data will be examined using an inductive approach through thematic analysis. A narrative approach will synthesise the quantitative and qualitative findings for a unified interpretation and comprehensive understanding of the results.Ethics and dissemination This protocol has been approved by the University of the Philippines Manila Research Ethics Board (UPMREB 2023-0579-01). The study findings will be disseminated through peer-reviewed journal publications and academic presentations at conferences.