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 with PCa 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.