Purpose Chronic pelvic pain syndrome (CPPS) is treated by use of various protocols. We compared tamsulosin monotherapy with tamsulosin in combination with antibiotics or anti-inflammatory agents and evaluated the efficacy of these treatments in patients with CPPS. Methods Patients (n=107) who were younger than 55 years and diagnosed with CPPS were randomly assigned to treatment with tamsulosin at 0.2 mg (group A), tamsulosin at 0.2 mg plus anti-inflammatory drugs (group B) or tamsulosin at 0.2 mg plus antibiotics (group C) daily. We applied the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (IPSS) to evaluate 100 patients who were treated for 12 weeks (7 withdrew). Scores of the three groups were compared by analysis of variance and we also evaluated subscores, which included pain, voiding and quality of life (QoL). Results All three groups showed statistically significant decreases in NIH-CPSI score, IPSS and subscore scores (P<0.05). There were no statistically significant differences between the groups except for the QoL domain of the IPSS (group A vs. C; P<0.01). Conclusions Tamsulosin monotherapy for 12 weeks was effective for treating patients with CPPS, compared with combination therapy with antibiotics or anti-inflammatory drugs.