Background: Phosphodiesterase type 5 inhibitors are commonly used for management of erectile dysfunction after prostate cancer (CaP) treatment. Single-institution studies have reported conflicting data on PDE5i use and recurrence after radical prostatectomy (RP). We re-evaluated the association between PDE5i use after RP and RT with biochemical recurrence in a nationwide, population-based registry. Methods: We performed a nested case-control study using data from the National Prostate Cancer Register of Sweden (including >98% prostate cancer cases nationwide), linked to the national Prescribed Drug Register. Among men with localized CaP who underwent primary RT or RP from 2006-2007 with 5 years of follow-up, we identified those with biochemical recurrence (n=293 cases). For each case, we identified 20 controls who were recurrence-free at the event date of the index case, using incidence density sampling stratified by age and treatment (n=5,767 controls). Multivariable conditional logistic regression was used to examine the relationship between overall PDE5i use and cumulative pill number with biochemical recurrence. Results: Among men treated by RT, PDE5i were not associated with BCR (OR 0.97, 95% CI 0.48-1.94), adjusting for marital status, education, income, PSA, clinical stage, Gleason score, and proportion of positive biopsies. As shown in the table, PDE5i were not associated with biochemical recurrence after RP adjusting for clinical features (OR 0.79, 95% CI 0.60-1.05), or with additional adjustment for surgical pathology (OR 0.83, 95% CI 0.62-1.10). Men whose cumulative number of PDE5i pills was above the median had a slightly lower risk of biochemical recurrence in the clinical model, and no difference in risk of biochemical recurrence after adjustment for RP features. Conclusions: Our results from a population-based setting suggest against an increased risk of biochemical recurrence among men using PDE5i after CaP treatment.