Purpose <p>To evaluate the efficacy and safety of aumolertinib in treating non-small cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM) and epidermal growth factor receptor (EGFR) mutations.</p> Methods <p>We conducted a retrospective analysis of clinical data from 79 patients with EGFR-mutated advanced NSCLC treated with aumolertinib after being diagnosed with LM at Shandong Cancer Hospital and Institute between April 2020 and July 2023. We evaluated overall survival (OS), progression-free survival (PFS), LM-PFS, and safety. Patient prognosis was assessed using Kaplan–Meier and Cox regression analyses.</p> Results <p>The median follow-up duration was 19.8 months (95% CI: 16.2–23.4), and 16 (20.3%) patients had previously used third-generation EGFR-TKI. The median LM-PFS was 10.6 months (95% CI: 8.6–12.5). The overall response rate (ORR) for LM was 53.2%, while the disease control rate (DCR) reached 91.1%. Among the 67 (84.8%) patients presenting with symptoms attributable to LM, 60 reported improved or stable symptoms. The median OS was 17.7 months (95% CI: 13.7–21.7), while the median PFS was 9.7 months (95% CI: 7.5–11.9). The systemic ORR and DCR were 38.0% and 87.3%, respectively. Multivariate Cox regression analysis identified L858R mutations (hazard ratio [HR] = 2.22, <i>P</i> = 0.030), prior systemic therapy (HR = 3.89, <i>P</i> &lt; 0.001), ECOG PS ≥ 2 (HR = 4.06, <i>P</i> &lt; 0.001) and ≥ 3 extracranial organ metastases (HR = 2.20, <i>P</i> = 0.025) as independent negative predictors of OS. Creatine kinase elevation (HR = 0.41, <i>P</i> = 0.018) was an independent predictor of better OS. Treatment-related adverse events occurred in 61 patients (77.2%), predominantly as grade 1 or 2.</p> Conclusion <p>Aumolertinib showed potential in treating EGFR-mutated NSCLC patients with LM, with a tolerable safety profile.</p>