Objective: We conducted a meta-analysis to explore all the potential risk factors for non-arteritic anterior ischemic optic neuropathy (NAION) based on the published literature.Methods: A comprehensive literature search through the online databases was performed to obtain studies concerning the risk factors of NAION up to June 2020. Pooled unadjusted odds ratios (ORs) or rate ratios (RRs) were calculated to evaluate the weight of risk factors. This study was registered in PROSPERO under the number CRD42018084960.Results: Our meta-analysis included 49 original studies comprising of more than 10 million patients. The following risk factors were proved to be significantly associated with NAION: male gender (OR = 1.67, 95% CI: 1.50–1.85, P < 0.00001), hypertension (RR = 1.28, 95% CI: 1.20–1.37, P < 0.00001), hyperlipidemia (RR = 1.43, 95% CI: 1.26–1.62, P < 0.00001), diabetes mellitus (DM) (RR = 1.53, 95% CI: 1.36–1.73, P < 0.00001), coronary heart disease (CHD) (RR = 1.68, 95% CI: 1.24–2.27, P = 0.0008), sleep apnea (RR = 3.28, 95% CI: 2.08–5.17, P < 0.00001), factor V Leiden heterozygous (RR = 2.21, 95% CI: 1.19–4.09, P = 0.01), and medication history of cardiovascular drugs.Conclusion: We concluded that the above risk factors were significantly related to NAION. Better understanding of these risk factors in NAION can help the direct therapeutic approaches.