Objective: To investigate the efficacy and safety of intravesical instillation of heparin/alkalized lidocaine (lidocaine mixed with sodium bicarbonate) combined with hydrodistension and transurethral fulguration in the treatment of female interstitial cystitis (IC). Methods: Female patients who attended the Department of Urology at the First Hospital of China Medical University between January 2012 and December 2020 and met the diagnostic criteria proposed in the guidelines of the American Urological Association with a new diagnosis of IC were selected for retrospective analysis. Cystoscopy and biopsy of suspicious lesions were performed at the time of diagnosis. All the patients were treated with an intravesical instillation regimen of 2% lidocaine 10 mL + 5% sodium bicarbonate 5 mL + heparin 25 000 IU for a continuous period of 12 months, with or without water dilatation and transurethral electrocautery according to the patient's preference, categorized as hydrodistension and transurethral fulguration (HD/TF) group and non-HD/TF group. The patients were evaluated before and 1, 6, and 12 months after treatment for O'Leary-Sant interstitial cystitis patient symptom index scores (ICSI), interstitial cystitis patient problem index scores (ICPI), visual analog scale (VAS) of suprapubic pain, and functional bladder capacity (FBC) changes. Results: A total of 79 patients were collected in this study. Four (5.1%) of these patients underwent cystectomy due to pathological diagnosis of cancer or treatment failure. The remaining patients were followed up 1, 6 and 12 months after treatment. Repeated-measures ANOVA showed a significant decrease in ICPI, ICSI and VAS and an increase in FBC after treatment compared with before treatment (P < 0.05). FBC continued to decrease during the 1, 6 and 12 months' post-treatment follow-ups, with statistically significant differences; ICSI continued to decrease during the 1 and 6 months post-treatment follow-ups, with statistically significant differences, while the difference between ICSI at 6 months post-treatment and at 12 months' post-treatment was not statistically significant. In the HD/TF group, ICPI continued to decrease in the follow-up from 1 and 6 months after treatment, and the difference was statistically significant, while the difference between ICPI 6 months after treatment and 12 months after treatment was not statistically significant. There was no statistically significant difference between the remaining indicators 1, 6 and 12 months after treatment. ICPI, ICSI, VAS and FBC improved earlier and the changes in VAS and FBC were more significant in the HD/TF group compared with the non-HD/TF group (P < 0.05). Conclusion: Heparin/alkalized lidocaine combination of intravesical instillation with hydrodistension and transurethral fulguration for IC is an effective treatment option. Heparin/alkalized lidocaine combination of intravesical instillation may be the first choice of treatment, which can significantly reduce the economic burden of patients and medical insurance system. If patients can accept it, transurethral fulguration with hydrodistension may be considered.