【Objective】 To explore the efficacy of a comprehensive treatment strategy of bladder hydrodistension, transurethral resection of bladder lesions and triple drug instillation in patients with painful bladder syndrome (BPS). 【Methods】 A total of 15 female BPS patients treated during Jan.2020 and Oct.2021 were enrolled. All patients received bladder hydrodistension and transurethral resection. After operation, intravesical instillation of a triple-drug mixture (2% lidocaine hydrochloride 20 mL, heparin sodium 25 000 U, and dexamethasone 10 mg) was administered once a day for 5 days, and then once per week for 4 weeks. The Visual Analogue Scale (VAS) score, quality of sexual life, health-related quality of life, and self-rating anxiety scale score were compared before treatment and 1, 4 and 12 weeks after treatment. The complications were recorded. 【Results】 All patients completed the treatment. Of 14 patients, the VAS score and self-rating anxiety scale score were lower in week 1, 4 and 12 after treatment, while the health-related quality of life score increased. One patient’s symptoms remained unchanged. The VAS score decreased from (5.47±1.81) to (1.87±1.51) (P<0.05), and the self-rating anxiety scale score decreased from (18.13±8.64) to (6.33±8.22) (P<0.05). The score of health-related quality of life increased from (24.47±5.41) to (31.53±6.49) (P<0.05). 【Conclusion】 The comprehensive strategy is effective in the treatment of bladder pain syndrome, which can relieve pain symptoms and improve patients’ quality of life.