Purpose: Chronic pelvic pain syndrome (CPPS) is the most common urogenital disease in middle aged men, and it shows various symptoms and a high recurrent rate. Uro-Vaxom® is effective for the treatment of urinary tract infection via the activation of the urothelial immune system. The main objectives of this study were to investigate the recurrence of CPPS and to find out if Uro-Vaxom® is helpful to suppress the recurrence of this condition. Materials and Methods: After completing treatment for CPPS (NIH-IIIa 45, NIH-IIIb 85), 130 patients were given a 12 week course of Uro-Vaxom® 60mg once a day before breakfast. Sixty patients were also included in the study as a control group after they completed the treatment for CPPS (NIH-IIIa 22, NIH-IIIb 38). All of patients were reevaluated 12 weeks and 24 weeks later with the NIH-CPSI criteria and the EPS findings. Results: The overall recurrent rate for NIH-IIIa disease was 22.7%, and it was 26.3% for the patients with NIH-IIIb disease in the control group, and it was 6.7% for the patients with NIH-IIIa disease and 7.1% for the patients with NIH-IIIb disease in the Uro-Vaxom® group (p<0.05). The classification of the recurrent CPPS was 46.7% NIH-IIIa and 53.3% NIH-IIIb in the control group, and 11.1% NIH-IIIa and 88.9% NIH-IIIb in the Uro-Vaxom® group. The possible predisposing factors related to the recurrence of CPPS were excessive alcoholic drinking (29.2%), overwork (25.0%) and stress (16.7%). In the non-recurrent patients, there was no change of the NIH-Chronic Prostatitis Symptom Index and the EPS findings for all patients during the follow-up period. Conclusions: There was about a 30% recurrence rate of CPPS within 6 months after treatment, and Uro-Vaxom® may play a significant role to suppress the recurrence of CPPS.