BackgroundBased on government estimates from the Asian Epidemic Model, new infections among men who have sex with men (MSM) and transgender women (TGW) in Thailand are forecast to proportionally increase over time. Daily oral Pre-exposure prophylaxis (PrEP) protects against HIV acquisition when used as prescribed. The “Princess PrEP” program is the first key population-led (PrEP) initiative under Thai royal patronage with an aim to scale up countrywide implementation of PrEP.MethodsRetention in and adherence to key population-led HIV PrEP services among HIV-uninfected Thai MSM and TGW was examined in four provinces: Bangkok, Chonburi, Chiang Mai, and Songkhla. HIV, HBsAg, creatinine tests, and self-administered questionnaires were performed during baseline measures. Participants were followed up after month 1, at month 3, then every 3 months. Correlates of nonadherence and loss to follow up at 1 month were assessed using linear regression models.Results37.4% of the participants reported low adherence to services (≤ 3 pills/week or missed clinic schedule at month 1). Factors associated with low adherence included younger age (25 years and under) (adjusted odds ratio (aOR): 1.49, 95% confidence interval (95% CI: 1.01–2.21, p = 0.044), being a TGW (aOR: 2.2, 95% CI: 1.27–3.83, p = 0.005), and whether the participant had not previously accessed services at the clinic (aOR = 1.68, 95% CI: 1.03–2.76, p = 0.04). Additionally, participants in Chonburi (the only TGW site) showed significantly lower adherence than those in the other three provinces (aOR: 2.91, 95% CI: 1.55–5.45, p = 0.001).ConclusionUrgent, innovative interventions for early PrEP adherence support among vulnerable sub-populations such as younger users, TGW, and new clients are needed to maximize prevention strategy in Thailand.Electronic supplementary materialThe online version of this article (10.1186/s12889-019-6645-0) contains supplementary material, which is available to authorized users.