Background: There are mixed results in surgical complications regarding the usage of prepectoral versus subpectoral implant placement in direct-to-implant breast reconstruction. This study aimed to provide a comprehensive synthesis of surgical complications between the subpectoral and prepectoral reconstructive method. Methods: PubMed, Embase, and Cochrane were searched for literature published up until December 2022. Studies that compared subpectoral and prepectoral breast reconstruction and reported at least one postoperative complication were included. The following 8 major outcomes were included: revision and reoperation, capsular contracture, explantation, seroma, hematoma, infection, skin necrosis, and animation deformity. Systematic review and meta-analysis were performed to compare outcomes of the 2 techniques. Subgroup analysis was performed to compare whether practice differences in different countries may have an impact on outcomes. Results: A total of 18 studies were identified in our literature search. Two thousand three hundred sixty patients were included, representing a total of 3135 breasts. Our analysis demonstrated that prepectoral reconstruction had significantly lower odds of developing postoperative hematoma [odds ratio (OR), 0.62; P = 0.05], seroma (OR, 0.67; P = 0.01), infection (OR, 0.64; P = 0.03), revision and reoperation (OR, 0.44; P < 0.00001), and animation deformity (OR, 0.01; P < 0.00001), compared with the subpectoral method. Subgroup analysis showed that differences between 3 countries (United States, Korea, Italy) are low (all subgroup heterogeneity test P > 0.1). Conclusions: While both subpectoral and prepectoral are safe methods for breast reconstruction, the prepectoral technique may lead to lower odds of developing multiple major postoperative complications.