PURPOSE: We determined the effect of a best evidence based monotherapeutic strategy for patients diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) referred to a specialized prostatitis clinic. MATERIALS AND METHODS: Patients with CP/CPPS referred by urologists after failure of prescribed therapy for evaluation and treatment at Queen's University prostatitis research clinic were extensively evaluated, aggressively treated following a standardized treatment algorithm and followed for 1 year using a validated prostatitis specific symptom and quality of life instrument, the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). All patients underwent a standardized protocol for CP/CPPS including a history, physical examination, standard 4-glass test, plus urethral swab and semen for microscopy and culture, uroflowmetry and residual urine determination. Treatment followed a best evidence based strategy with a standardized monotherapy based algorithm. RESULTS: A total of 100 consecutive patients with CP/CPPS (average age 42.2 years, range 20 to 70 and average symptom duration 6.5 years, range 0.5 to 39) had 1-year followup after initial evaluation. Patients were prescribed treatment based on documentation of "failed," "successful" and "never tried" therapies based on a standardized treatment algorithm. Patients treated successfully were continued on the prescribed therapy, while therapy was discontinued and new therapy instituted (based on algorithm) in those in whom the initially prescribed therapy failed. At 1 year there was a statistically significant decrease in total NIH-CPSI (23.3 to 19.5, p = 0.0004), pain (11.0 to 9.4, p = 0.03) and quality of life (7.7 to 6.1, p <0.001), but not voiding (4.6 to 4.0, p = 0.12). A perceptible 25% decrease in total NIH-CPSI symptom score was noted in 37% and the greatest improvement was in the quality of life domain (43% of patients had greater than 25% improvement in quality of life). Of the patients 35% had a significant decrease of greater than 6 points in total NIH-CPSI. A clear, clinically significant improvement in total NIH-CPSI (greater than 50% decrease) was noted in 19%. CONCLUSIONS: Approximately a third of patients with treatment refractory CP/CPPS undergoing extensive evaluation and therapy based on a sequential monotherapy treatment strategy in a specialized prostatitis clinic had at least modest improvement in symptoms during 1 year. This study confirms that a treatment strategy based on the sequential application of monotherapies for patients with a long history of severe CP/CPPS remains relatively poor.