Objective: To investigate the clinical significance of cadherin 13 (CDH13) gene promoter methylation in the serum of patients with prostate cancer. Methods: This prospective study examined the methylation status of CDH13 in serum samples obtained from patients with primary prostate cancer and age-matched control subjects, using methylation-specific polymerase chain reaction. Associations between methylation status of CDH13 and various clinicopathological features and patient survival were evaluated. Results: A total of 98 patients with prostate cancer and 47 control subjects were enrolled in the study. CDH13 promoter methylation was detected in 44 out of 98 (44.9%) patients with prostate cancer; no methylation was found in control subjects. Methylation of CDH13 was significantly associated with an increased Gleason score, an advanced tumour stage, and a high prostate-specific antigen level. CDH13 methylation was associated with a worse survival outcome and a relative risk of death of 6.132 (95% confidence interval: 3.160, 12.187). Conclusions: Promoter methylation of CDH13 occurred frequently in the serum of patients with prostate cancer, was associated with an increased risk of death, and may become a useful independent predictor of a poor prognosis.