Background: Prostate cancer (PC) is associated with a high clinical and economic burden. Advanced oral (AO) therapies have become the standard of care for patients with advanced PC, but real-world data on treatment patterns and their impact on healthcare resource utilization (HRU) are lacking. This study aims to describe treatment adherence, factors associated with adherence, and its impact on HRU in patients with PC initiated on AOs. Methods: Adults with a PC diagnosis initiated on apalutamide, enzalutamide, or abiraterone acetate were identified using Symphony Health Solutions Patient Transactional Databases (10/01/2014-09/30/2019). Patients were included if they had ≥6 months of continuous clinical activity before and after AO initiation (index date) and no other cancer diagnoses. Adherence was defined using the proportion of days covered (PDC) by AOs during the 6-month period following the index date. Patients with a PDC≥80% were considered adherent. Multivariable logistic regression was used to evaluate baseline characteristics associated with AO adherence. All-cause and PC-related HRU was assessed from 6 to 18 months post-index and compared between adherent and non-adherent patients using multivariable Poisson regression. Results: A total of 27,322 patients initiated on an AO were identified. Most patients were aged ≥65 years (81%), were white (60%), had Medicare coverage (48%), and had metastatic PC (56%). At 6 months, 57% of patients were adherent to AOs. Patients aged 55-64 and 65-74 years had greater odds of being adherent versus those aged ≥75 years (24% and 22%, respectively), while Black patients had 17% lower odds of being adherent relative to white patients (all p<0.01). Medicare coverage was associated with 23% greater odds of being adherent relative to commercial insurance (p<0.01). Patients with a below median primary insurer paid amount for their first AO claim had 13% greater odds of being adherent relative to the above median amount (p<0.05). Adherent patients generally had fewer HRU compared to non-adherent patients. More specifically, adherent patients had 25% fewer all-cause inpatient days, 16% fewer all-cause emergency room (ER) visits, 18% fewer all-cause other non-outpatient services use, as well as 30% fewer PC-related inpatient days and 24% fewer PC-related ER visits (all p<0.01) relative to non-adherent patients. Conclusions: In this study, non-adherence over a 6-month period following AO initiation was associated with substantially higher HRU, including inpatient and ER visits. Moreover, non-adherence was widely observed, impacting over 40% of advanced PC patients in the first 6 months after AO initiation. Identifying factors linked to lower adherence and defining strategies to improve adherence may improve patient outcomes and associated medical resource utilization. (1)Abiraterone acetate plus prednisone is the approved therapy although the combination was not imposed.