48 Background: Racial disparities in prostate cancer (PCa) incidence, health-related quality of life (HRQoL), treatment outcomes, and decisional regret have been reported. This study evaluated decision-making in African American (AA) and Caucasian (CA) patients with localized PCa to better understand HRQoL domains associated with post-treatment regret. Methods: This is a prospective cohort study evaluating patients with low- and intermediate-risk PCa in a racially diverse, equal access health-care setting who enrolled in a multidisciplinary clinic at Walter Reed National Military Medical Center. Demographic, clinical, and treatment outcomes data were collected. Validated questionnaires were administered, including the Control Preferences scale, Decision Regret scale (DRS), Expanded Prostate Cancer Index Composite (EPIC), and Medical Outcomes Study Short Form (SF36). Questionnaires were given at fixed intervals post-treatment. Results: A total of 297 (37.8%) AA and 489 (62.2%) CA patients were included in this study. AA patients were more likely to elect radiation therapy (RT) and less likely to elect radical prostatectomy (RP) or active surveillance. AA patients preferred more physician involvement in decision-making. Significantly higher regret was observed for AA patients after RP at 6 and 24 months, compared to CA patients. Only 6-month urinary bother was associated with regret in AA patients while, among CA patients, regret was associated with mental health and sexual bother. Among XRT patients, multiple HRQoL domains were associated with regret in AA patients, while only 36-month mental health was associated with regret in CA patients. Conclusions: Several key differences were noted across race in terms of HRQoL domains that were associated with patient regret. This cohort is now being followed for patient satisfaction with medical care. Such data may further help physicians tailor conversations with patients during treatment decision making to optimize HRQoL and minimize regret.