INTRODUCTION: Transgender women (TGW) need a specific package of primary care services usually not available in the publicly funded healthcare system. In addition, little is known about HIV and syphilis prevalence and incidence in clinic-based samples of TGW. Here we evaluate the uptake of a transgender-specific package of primary care services by TGW in Bangkok, Thailand and assess HIV and syphilis prevalence and incidence among them. METHODS: Open cohort study of TGW attending services at the Tangerine Community Health Clinic from 2016 to 2019. Cross-sectional and longitudinal analysis of routinely collected clinic data was performed to study trends in the number of clients, clinic visits and HIV and syphilis prevalence and incidence. RESULTS: During the study period, 2947 TGW clients made a total of 5227 visits to Tangerine. The number of clients significantly increased from 446 in 2016 to 1050 in 2019 (p < 0.001) and the number of visits from 616 to 2198 during the same period (p < 0.001). Prevalence of HIV at first visit was 10.8% and of syphilis 9.8%. HIV incidence was 1.03 per 100 person years (PY) and of syphilis 2.06 per 100 PY of follow-up. From 2016 to 2019, significant decreases occurred in the annual prevalence of HIV from 14.6% to 9.9% (p < 0.01). The annual prevalence of syphilis significantly increased from 6.6% in 2016 to 14.6% in 2018, and then decreased to 7.3% in 2019 (p < 0.001). The annual HIV incidence decreased during 2016 to 2019, from 1.68 to 1.28 per 100 PY, but this reduction was not statistically significant. The annual incidence of treponemal test seroconversion significantly increased from zero in 2016 to 4.55 per 100 PY in 2019 (p < 0.001). CONCLUSIONS: The increasing uptake of a transgender-specific package of services, including co-located gender affirmative hormone therapy, suggests this may be an effective model in engaging and retaining TGW in primary care. The decrease in HIV prevalence and low HIV incidence across calendar years point at a possible reduction of HIV acquisition among the TGW population served by Tangerine. The increasing prevalence of syphilis suggests ongoing high-risk sexual behaviour and underscores the need for screening and treatment for this infection at the time of delivery of HIV services.