To investigate the clinical significance of cadherin 13 (CDH13) gene promoter methylation in the serum of patients with prostate cancer. 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. 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). 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.