ABSTRACT Aim Sacral neuromodulation (SNM) is widely recognized as the essential treatment modality for patients suffering from various lower urinary tract disorders, particularly overactive bladder (OAB). This prospective study recruited patients who underwent variable frequency SNM treatment at six Chinese medical centers, aiming to evaluate the gender‐specific effects of this intervention and provide precise guidance on its application for clinical management. Methods This prospective study was managed by Beijing Hospital, and six Chinese medical centers participated in this prospective research. Inclusion and exclusion criteria were established to screen patients based on the indication for SNM. During the research, all patients were required to record 72‐h voiding diaries, urgency scores, and visual analogue scale (VAS) scores to reflect their disease symptoms. Additionally, subjective questionnaire surveys such as OAB symptom score (OABSS) and quality‐of‐life (Qol) score were recorded to reflect the patients' quality of life and treatment satisfaction. Results In this study, 52 patients (male patients: 25; female patients: 27) with OAB symptoms agreed to undergo variable frequency stimulation SNM therapy and finally convert to Stage II. Regarding the baseline outcomes, no significant differences were observed between the male and female groups. In terms of postoperative indicators, male patients showed a greater improvement in Qol scores compared to their female counterparts (20.06 ± 13.12 vs. 40.83 ± 26.06, p = 0.005). The results from VAS scores indicated that pain remission was more pronounced in male patients than in female patients (0.31 ± 0.87 vs. 1.67 ± 2.16, p = 0.02). Importantly, there was a statistically significant disparity in urinary urgency between males and females (male patients: 1.19 ± 1.56; female patients: 2.17 ± 1.52, p = 0.04). Conclusions In our study, we found that variable frequency SNM treatment yielded sex‐specific differences in therapeutic effects, with male patients having a better outcome in some metrics. This suggests that a patient's sex may influence when variable frequency SNM is used, and in the patient's follow‐up. Trial Registration ClinicalTrials.gov identifier: ChiCTR2000036677.