Background In cases of total knee arthroplasty (TKA) threatened by potential hardware exposure, flap-based reconstruction is indicated to provide durable coverage. Historically, muscle flaps were favored as they provide vascular tissue to an infected wound bed. However, data comparing the performance of muscle versus fasciocutaneous flaps are limited and reflect a lack of consensus regarding the optimal management of these wounds. The aim of this study was to compare the outcomes of muscle versus fasciocutaneous flaps following the salvage of compromised TKA. Methods A systematic search and meta-analysis were performed to identify patients with TKA who underwent either pedicled muscle or fasciocutaneous flap coverage of periprosthetic knee defects. Studies evaluating implant/limb salvage rates, ambulatory function, complications, and donor-site morbidity were included in the comparative analysis. Results A total of 18 articles, corresponding to 172 flaps (119 muscle flaps and 53 fasciocutaneous flaps) were reviewed. Rates of implant salvage (88.8% vs. 90.1%, P=0.05) and limb salvage (89.8% vs. 100%, P=0.14) were comparable in each cohort. While overall complication rates were similar (47.3% vs. 44%, P=0.78), the rates of persistent infection (16.4% vs. 0%, P=0.14) and recurrent infection (9.1% vs. 4%, P=0.94) tended to be higher in the muscle flap cohort. Notably, functional outcomes and ambulation rates were sparingly reported. Conclusions Rates of limb and prosthetic salvage were comparable following muscle or fasciocutaneous flap coverage of compromised TKA. The functional morbidity associated with muscle flap harvest, however, may support the use of fasciocutaneous flaps for coverage of these defects, particularly in young patients and/or high-performance athletes.