Approximately 20-30% of women suffer from recurrent cystitis. Recently, the problem of bacterial internalization, especially by Escherichia coli, has been significantly emerging as the main cause of recurrent episodes. It is believed that such a process is favored by damage to the urothelial mucous membrane. Concerning this, intravesical therapy with hyaluronic acid alone or in association with chondroitin sulfate was shown to improve urothelium thickness and reduction of bacterial load in the urine. The aim of our study was to assess whether intravesical therapy with hyaluronic acid (HA) and chondroitin sulfate (CS) is more effective than antibiotic therapy in reducing episodes and symptoms of recurrent urinary tract infections. We compared the number of recurring episodes in three groups of patients affected by recurrent urinary tract infections assigned to three different therapeutic regimens: the first group was treated only with HA and CS, the second group with HA and CS associated with fosfomycin, and the third group was treated only with fosfomycin (F). We assessed the number of recurrent episodes for each patient that occurred during a 6- to 12-month follow-up. The results showed 72.7% of patients in the HA-CS group, 75% in the fosfomycin + HA-CS group, and only 30.4% in the fosfomycin group were event free at follow-up. The results were analyzed using the Fisher's exact test. In conclusion, intravesical therapy with hyaluronic acid and chondroitin sulfate is an effective therapeutic approach to treat and prevent episodes of recurrent cystitis.