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To determine whether epididymo-orchitis, a common infectious disease among men, is associated with subsequent prostate cancer (PCa) via a nationwide cohort study.This nationwide population-based study of patients treated from 2001 to 2013 included a total of 4991 patients with epididymo-orchitis as the study group and 19,922 matched patients without epididymo-orchitis as a control group. We tracked the patients in both groups for a 5-year period to identify any new cases of PCa. Cox proportional hazards regressions were performed to calculate the hazard ratio (HR) of PCa during this 5-year follow-up period.Of the 24,913 patients in the study, 235 (0.9%) were newly diagnosed with PCa during the 5-year follow-up period; 77 (1.5%) of those were from the epididymo-orchitis group and 158 (0.8%) were from the control group. Compared to the patients without epididymo-orchitis, the adjusted HR for PCa for the patients with epididymo-orchitis was 1.56 (95% confidence interval [CI]: 1.18–2.06) during the 5-year follow-up period. Ages of more than 70 years, higher incomes, hypertension, and hyperlipidemia were more strongly associated withPCa in the study group than in the control group.The results were associated with a 56% increased risk for PCa among patients with epididymo-orchitis. Epididymo-orchitis may play an etiological role in the development of PCa in Asian populations. Further studies are warranted, however, to investigate the relationship between epididymo-orchitis and PCa.