© 2020, The International Urogynecological Association.Introduction and hypothesis: To investigate the long-term feasibility, safety and effectiveness of intravesical chondroitin sulfate therapy in patients with one or more forms of chronic cystitis. Methods: The study included 62 female patients with interstitial cystitis/painful bladder syndrome (IC/PBS) who received intravesical chondroitin sulfate (40 ml/80 mg) therapy between 2014 and 2018. A total of 15 doses of intravesical treatment were applied, once weekly in the first month and once monthly from the second month onward. A 3-day voiding diary, a visual analog scale (VAS), the O'Leary Sant Indexes (ICSI/ICPI), the Pelvic Pain and Urgency/Frequency Symptom (PPUFS) Scale and PPUF Bother scores were recorded and evaluated through prospective comparison before treatment and at the first month and first year. Patients were also assessed using the Global Response Assessment (GRA) at the end of the first month and first year to assess the effectiveness of responses to treatment. Results: In the first month of treatment, 0.2% chondroitin sulfate was ineffective in 22.5% of patients, with mild improvement observed in 40.0% and moderate-good improvement in 37.0%. Evaluation at the end of the first year revealed mild improvement in 21.0% of patients and moderate-good improvement in 79.0%. Statistically significant improvements were observed in all scoring systems at 1 and 12 months compared with pre-treatment values (p < 0.001). Conclusion: Long-term intravesical chondroitin sulfate therapy is a safe and highly successful therapeutic modality that produces significant improvement in patients’ quality of life and symptoms in the treatment of IC/PBS.