Background <p>The application value of intraoperative lateral spreading response (LSR) during microvascular decompression (MVD) is always disputed. The current study aimed to explore the predictive value of intraoperative LSR monitoring for the long-term outcome in patients with primary hemifacial spasm (pHFS).</p> Methods <p>The data from 312 pHFS patients were retrospectively reviewed. The zygomatic LSR (ZYG-LSR) and mandibular LSR (MAN-LSR) monitoring were performed during surgery. The correlations of ZYG-LSR and MAN-LSR disappearances with patients’ long-term outcomes (one year after surgery) were retrospectively investigated. Consequently, binary logistic regression analysis was applied to explore their predictive value. Finally, the implications of their combined utilization for predicting the long-term outcome were explored.</p> Results <p>Patients with either persistent ZYG-LSR or MAN-LSR exhibited a higher incidence of spasms one year after surgery (<i>p</i> &lt; 0.001). Persistent ZYG-LSR (odds ratio 7.721, <i>p</i> &lt; 0.001) and MAN-LSR (odds ratio 10.729, <i>p</i> &lt; 0.001) were both identified as independent predictive factors for an unfavorable long-term outcome. Taking both ZYG-LSR and MAN-LSR into consideration, patients with simultaneously disappeared two waves had the highest long-term recovery rate (97.2%), followed by patients with either persisted wave (76.5%) and patients with simultaneously persisted two waves (27.3%). The differences among all pairwise comparisons were statistically significant (<i>p</i> &lt; 0.001 for all).</p> Conclusion <p>The current study confirmed the application value of intraoperative LSR monitoring during MVD in patients with pHFS. In addition, the clinical significance of two-branch LSR monitoring was also described. The findings can provide important insights for optimizing the application of intraoperative LSR monitoring in clinical practice.</p>