Purpose: In this study the authors aimed to assess the efficacy of intravesical hyaluronic acid (HA) instillation in patients with resistant painful bladder syndrome (PBS). Materials and Methods: A series of 32 women with PBS received intravescical instillation of HA once-a-week for eight weeks and then once monthly for four months for a total of 12 doses. The authors considered scale (VAS) pain scores ≥ 4 and total scores (symptom and bother scores) ≥ 13 on the pelvic pain and urgency/frequency (PUF) questionnaire. An efficacy of the HA instillation was evaluated by comparing the mean changes in the scores of the VAS and questionnaires from baseline to eight weeks of treatment. Improvement was defined as a ≥ 2 decrease in the VAS. Results: The authors compared the responses at baseline and after treatment: there were 22 patients (63.0%) with positive response rate at week 8, which was maintained until 12 months. Specifically, both VAS and PUF score decreased significantly after treatment. Conclusion: The present results showed that intravesical HA therapy is an effective treatment for patients with PBS who had inadequate response to conservative treatment.