PURPOSE: Adherence to pre-exposure prophylaxis (PrEP) during periods of PrEP-indication (i.e., prevention-effective adherence) is critical for preventing HIV. We sought to describe factors associated with prevention-effective adherence trajectories among transgender women (TW) to inform PrEP implementation strategies. METHODS: Using data from The LITE American Cohort (n = 728), we performed group-based multi-trajectory modeling (GBMTM) to identify clusters of TW with similar trajectories of PrEP adherence and indication, and sociodemographic, biobehavioral, and structural correlates of each trajectory. RESULTS: We identified five trajectories: (1) consistent indication/no PrEP (15.3%), (2) initial indication/no PrEP (47.1%), (3) declining indication/discontinued PrEP (9.5%), (4) consistent indication/PrEP adherent (18.5%), and (5) increasing indication/initiated PrEP (9.6%). TW diagnosed with an STI were more likely to follow a consistent indication/no PrEP trajectory compared to consistent indication/PrEP adherent trajectory (adjusted Relative Risk Ratio [aRRR], 2.54; 95% confidence interval [CI], 1.16-5.57). TW who experienced homelessness were more likely to follow PrEP discontinuation and initiation trajectories relative to PrEP adherence (aRRR, 2.71; 95% CI, 1.10-6.70 and 2.83; 95% CI, 1.13-7.05, respectively). CONCLUSIONS: Over a quarter of TW followed trajectories suggestive of prevention-effective adherence, while 15% did not initiate PrEP despite consistent indication. Findings highlight missed opportunities for PrEP engagement at STI diagnosis and suggest structural interventions addressing housing instability may improve prevention-effective adherence among TW.