Objective: To investigate the clinical significance of protocadherin-8 (PCDH8) promoter methylation in bladder cancer. Methods: Methylation-specific polymerase chain reaction was used to examine the promoter methylation status of PCDH8 in tumour tissue samples obtained from patients with bladder cancer, and in normal bladder epithelial tissue samples obtained from age-and sex-matched control subjects. Methylation status was correlated with demographic, clinical and pathological parameters and disease outcome. Results: PCDH8 promoter methylation was detected in 76/135 (56.3%) patients with bladder cancer and none of 34 (0%) control subjects. Methylation was significantly associated with advanced stage (T 2 -T 4 ), high grade (G 3 ), tumour recurrence, larger tumour diameter (>3 cm) and nonpapillary morphology. In addition, methylation was associated with significantly shorter survival time and was an independent predictor of overall survival. Conclusions: PCDH8 promoter methylation is a common occurrence in bladder cancer, and is associated with malignant behaviour and poor prognosis. Determination of PCDH8 promoter methylation status in tumour tissue may assist in the identification of patients who require aggressive postoperative intervention in order to improve prognosis.