Background: Financial toxicity (FT), a patient-reported outcome measure (PROM) is defined as the detrimental impact of financial burden caused by a cancer diagnosis on a patient’s well-being. FT is common among cancer patients, yet little is known about FT following radical prostatectomy (RP) for prostate cancer in countries with universal health coverage. We aimed to assess de novo FT and its impact on health-related quality of life (HRQOL) in a large prospective cohort of patients undergoing RP with a systematic follow-up of up to 10 yrs. Methods: 2254 consecutive patients who underwent RP at a large tertiary care center were analyzed. PROMs were prospectively assessed preoperatively, postoperatively at 3mo, then annually until a maximum follow-up of 120mo, applying the validated EORTC QLQ-C30- and the prostate cancer-specific QLQ-PR25 questionnaires. FT was assessed by the “financial toxicity subscale” (FTS) of the EORTC QLQ-C30. Based on previous reports, meaningful FT was defined as FTS ≥ 17. Multivariable regression analysis was used to identify predictors for the development of de novo FT. Separate modeling of longitudinal HRQOL was performed for patients with de novo FT (FT-cohort) and without FT (no-FT-cohort). General HRQOL was assessed by the global health status domain (GHS) of the EORTC QLQ-C30. Results: 298 patients reporting FT prior RP were excluded from further analysis. 20.3% (n=397) of the included patients reported de novo FT within 12 months after RP with a mean FTS-score of 47.3 (SD 21.9). Baseline clinicopathological characteristics did not differ between the FT-cohort and the no-FT-cohort (p-range .060-.173). Multivariable logistic regression analysis revealed subsequent therapies following RP (OR 1.981, 95%CI 1.11-3.53, p=.020), low preoperative emotional functioning (OR 0.990, 95%CI 0.92-0.99, p=.031) and low preoperative social functioning (OR 0.990, 95%CI 0.98-0.99, p=.035) to independently predict development of de novo FT after RP. In longitudinal analysis, significantly worse general HRQOL was observed for patients with de novo FT postoperatively and up to 48mo after RP (p-value each < .001). In the longer term, both cohorts reported no significant difference in general HRQOL up to 10yrs post RP (p-range: .90 - .91). Conclusions: The current study provides prospective data from a unique contemporary patient cohort, which reveals independent predictors for de novo FT in prostate cancer patients following RP. Furthermore, it displays the natural course of general HRQOL for patients who develop de novo FT.