Complex head and neck defects involving composite defects can be reconstructed using chimeric flaps or multiple flaps with separate anastomoses. Limited comparisons exist between chimeric and multiple flap reconstructions. We compare outcomes between chimeric and multiple flap reconstructions in oral cavity reconstruction. PubMed (NLM), Embase (Elsevier), Web of Science (Clarivate Analytics), and Cochrane CENTRAL (Wiley). A systematic review was conducted, including English articles reporting outcomes of oral cavity reconstruction with either chimeric flaps or multiple flaps. Data extraction included patient characteristics, flap type, and outcomes such as flap survival, partial flap loss, operating room time, hospital length of stay, and postoperative complications. Forty-seven articles comprising 1435 patients were included. Notably, 552 patients underwent multiple flaps, while 883 received chimeric flaps. Meta-analysis revealed no statistically significant difference in flap survival between chimeric and multiple flap patients (98% vs. 99%, p = 0.198). Multiple flap patients had higher rates of operating room take-backs for anastomotic issues and longer hospital stays compared with chimeric flap patients. There were no significant differences in partial flap failure, resumption of diet and speech, need for subsequent flaps, fistula formation, or general complications. This large-scale meta-analysis demonstrates equivalent flap survival between chimeric and multiple flaps in the reconstruction of composite oral cavity defects. Both approaches appear to be safe and acceptable, with comparable outcomes in terms of diet and speech resumption, rates of fistulization, and general postoperative complications. Multiple flap patients had higher rates of operating room take-backs and longer hospital stays. NA Laryngoscope, 134:4196-4202, 2024.