BACKGROUND: Leptomeningeal collateral status is a major determinant of outcomes in patients with acute ischemic stroke; however, the factors that determine collateral status are not well understood. We conducted a comprehensive systematic review and meta-analysis to identify determinants associated with collateral status in patients with anterior circulation infarction. METHODS AND RESULTS: The PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched for studies that reported the determinants of leptomeningeal collateral status in acute ischemic stroke between January 2000 and June 2023. A random-effects meta-analysis model was used to pool the determinants of leptomeningeal collateral status. Eighty-one studies with 17 366 patients met the inclusion criteria. We analyzed 31 potential risk factors, and the results indicated that worse leptomeningeal collateral status was significantly associated with older age (weighted mean difference, 1.22 [95% CI, 0.69 to 1.76]), male sex (odds ratio [OR], 1.12 [95% CI, 1.02 to 1.23]), hypertension (OR, 1.27 [95% CI, 1.15 to 1.40]), diabetes (OR, 1.21 [95% CI, 1.10 to 1.33]), atrial fibrillation (OR, 1.26 [95% CI, 1.09 to 1.46]), cardioembolic stroke (OR, 1.27 [95% CI, 1.04 to 1.55]), internal carotid artery occlusion (OR, 1.84 [95% CI, 1.50 to 2.25]), and higher admission blood glucose (weighted mean difference, 8.74 [95% CI, 2.52 to 18.51]). CONCLUSIONS: Hypertension and diabetes could be modifiable risk factors associated with leptomeningeal collateral status. Older age and male sex could be nonmodified risk factors. Further high-quality therapeutic studies focusing on controlling risk factors are needed to support our findings.