This systematic review and meta-analysis compared the safety and effectiveness of minimally invasive adrenalectomy (MIA) with open adrenalectomy (OA) in patients with large adrenal tumors (≥5 cm).We performed a systematic review and cumulative meta-analysis of the primary outcomes according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. Five databases including Medline, PubMed, Cochrane Library, Scopus, and Web of Science were systematically searched. The time frame of the search was set from the creation of the database to March 2022.Ten studies including 898 patients were included. Compared to OA, MIA is superior for length of stay [LOS WMD = -3.52, 95% CI (-4.61, -2.43), P < 0.01], drainage time [DT WMD = -0.68, 95% CI (-1.27, -0.09), P < 0.05] and fasting time [FT WMD = -0.95, 95% CI (-1.35, -0.55), P < 0.01], estimated blood loss [EBL WMD = -314.22, 95% CI (-494.76, -133.69), P < 0.01] and transfusion [WMD = -416.73, 95% CI (-703.75, -129.72), P < 0.01], while operative time (OT) and complications are not statistically different. For pheochromocytoma, MIA remains superior for LOS [WMD = -3.10, 95% CI (-4.61, -1.60), P < 0.01] and EBL [WMD = -273.65, 95% CI (-457.44, -89.86), P < 0.01], while OT and complications are not significantly different.MIA offers advantages over OA in the management of large adrenal tumors, including in the case of a specific large adrenal tumor - large pheochromocytoma.Copyright © 2022. Published by Elsevier Ltd.