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Background/Objective Drug-resistant epilepsy (DRE) is a chronic and disabling neurological condition affecting many millions worldwide. Non-invasive neuromodulation (NIN) is a promising treatment for DRE. However, multiple methods exist and evidence for efficacy is heterogeneous and difficult to compare. In this review, for the first time, we performed a systematic review and meta-analysis addressing outcomes from all major NIN modalities.Methods We performed a systematic review of efficacy and safety outcomes of NIN in DRE using the PRISMA guidelines. PubMed, OVID Medline, OVID Embase and Web of Science were searched.Results 54 studies were included, comprising investigations on six NIN modalities: repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), low-intensity focused ultrasound (LI-FUS), transcutaneous vagus nerve stimulation (tVNS) and trigeminal nerve stimulation (TNS) in DRE. The responder rate (RR) for rTMS was 33% (95% confidence interval (CI): 15–51%) versus 4% (95% CI: -1–9%) in controls; with a responder status odds ratio (OR) of 8.60 (95% CI: 1.26–58.7, p=0.028). For tDCS, the RR was 41% (95% CI: 27–56%) and 12% (95% CI: -1–25%) in controls; with a responder status OR of 5.40 (95% CI: 0.59–49.5, p=0.14). Insufficient tACS and LI-FUS studies met inclusion criteria. For tVNS, the RR was 34% (95% CI: 7.8–59%) and 45% for TNS (95% CI: 28–61%) at 24 weeks. No serious adverse events were reported.Conclusion rTMS is a safe and potentially effective adjunctive therapy in DRE. More conclusive evidence is required for the remaining NIN modalities.