Introduction Although HIV prevalence among transgender women who have sex with men in Vietnam is high (16–18%), uptake of pre‐exposure prophylaxis (PrEP) is low compared to other populations. When PrEP was initiated in 2017, gender‐affirming healthcare was largely unavailable. Lack of access to competent, stigma‐free healthcare is a well‐documented barrier to transgender women's uptake of PrEP and primary healthcare (PHC). We aimed to demonstrate the utility of a PrEP quality improvement intervention in pinpointing and addressing barriers to PrEP use among transgender women in Vietnam. Methods We applied a real‐world participatory continuous quality improvement (CQI) and Plan‐Do‐Study‐Act (PDSA) methodology to ascertain barriers to PrEP uptake among transgender women and determine priority actions for quality improvement. A CQI team representing transgender women leaders, key population (KP)‐clinic staff, public‐sector HIV managers and project staff applied PDSA to test solutions to identified barriers that addressed the primary quality improvement outcome of the monthly change in PrEP uptake among transgender women and secondary outcomes, including month‐3 PrEP continuation, the impact of offering PHC on PrEP uptake and unmet PrEP need. We utilized routine programmatic data and a descriptive cross‐sectional study enrolling 124 transgender women to measure these outcomes from October 2018 to September 2021. Results Five key barriers to PrEP uptake among transgender women were identified and corresponding solutions were put in place: (1) offering gender‐affirming care training to KP‐clinics and community‐based organizations; (2) integrating gender‐affirming services into 10 KP‐clinics; (3) offering PHC through five one‐stop shop (OSS) clinics; (4) implementing a campaign addressing concerns related to hormone use and PrEP interactions; and (5) developing national HIV and transgender healthcare guidelines. New PrEP enrolment and month‐3 PrEP continuation increased significantly among transgender women. Of 235 transgender women who initially sought healthcare other than PrEP at OSS clinics, 26.4% subsequently enrolled in PrEP. About one‐third of transgender women reported unmet PrEP need, while two‐thirds indicated an interest in long‐acting cabotegravir. Conclusions Offering gender‐competent, integrated PHC can increase PrEP enrolment and continuation, and can be an entry‐point for PrEP among those seeking care within PHC clinics. More work is needed to expand access to transgender women‐led and ‐competent healthcare in Vietnam.