Purpose of Investigation: To compare the efficacy and safety of intravesical instillation of hyaluronic acid/chondroitin sulfate with conventional long-term antibiotic prophylaxis in women with recurrent bacterial cystitis. Materials and Methods: In this analysis of a prospective study, where women with recurrent bacterial cystitis were randomised to intravesical hyaluronic acid 800 mg/chondroitin sulfate 1,000 mg (group 1) or long-term antibiotic prophylaxis (group 2 – control group), patients in group 1 were evaluated 36 months after treatment. Outcomes included cystitis recurrence, subjective pain symptoms based on a visual analogue scale (VAS), three-day voiding, pelvic pain and urgency/frequency symptoms (PUF scale), sexual function questionnaire, quality of life based on King’s Health Questionnaire (KHQ), maximum cystometric capacity (MCC), and adverse events. Results: Twelve women (mean ± standard deviation 59.3 ± 13.9 years old) underwent follow-up at 36 months after treatment. There were improvements in all efficacy evaluations at 36 months’ follow-up, with significantly favourable mean changes from baseline in cystitis frequency (–5.4 episodes/year; p < 0.001), three-day voiding (–10.7 voids; p = 0.002), urinary VAS (–6.7 points; p < 0.001), PUF (–14.2 points; p < 0.001), sexual function (–4.3 points; p < 0.001) and KHQ (–34.0; p < 0.001) scores, and MCC (+131.7; p < 0.001). No adverse events were reported. Conclusions: Intravesical hyaluronic acid/chondroitin sulfate significantly reduced cystitis recurrence and associated symptoms and was well tolerated in women with recurrent bacterial cystitis at 36 months’ after treatment.