Introduction. Wound breakdown following total knee arthroplasty (TKA) increases the risk of device exposure, infection, and major amputation. Although a variety of options to facilitate coverage of compromised knee joint prostheses exist, the relative safety, efficacy, and functional impact of each has not been determined. Objective. This study aims to identify those perioperative factors that influence reconstructive and functional outcomes in patients with periprosthetic TKA defects. Materials and Methods. A 5-year retrospective review of outcomes following surgical management of TKA wounds was undertaken. Data pertaining to the timing of presentation, type and frequency of operative interventions, rates of implant/limb salvage, ambulatory status, visual analogue scores (VAS) for pain, and complications were collected. Results. Thirty patients were identified during the study period with a mean follow-up of 20 months. Rates of limb salvage (66.7% vs. 91.7% vs. 75% vs. 0%, P < .001) and postoperative ambulation (100% vs. 83.3% vs. 75% vs. 54.5%, P = .036) were significantly different between patients who underwent primary closure, local muscle flap coverage, free tissue transfer coverage, and above-the-knee amputation, respectively. The number of debridements prior to definitive closure did not significantly influence rates of limb salvage (P = .21). Active tobacco use (odds ratio [OR], 4; 95% confidence interval [CI], 1.13-14.2; P = .03) and time to initial presentation from the index joint replacement (OR, 0.99; 95% CI, 0.9-1.0; P = .04) adversely impacted device salvage. Both of these factors similarly influenced the overall likelihood of limb salvage (OR, 6.5; 95% CI, 1.5-28.8; P = .01; OR, 0.99; 95% CI, 0.99-1.0; P = .04). The VAS scores were not significantly different between index closure types (P = .77) but were significantly lower for patients who required < 10 debridements prior to definitive closure (P = .02). Conclusions. Early intervention with limited-frequency, and thorough debridement and prompt soft tissue coverage optimizes the chances of functional limb salvage in patients with complex periprosthetic TKA wounds. These findings may inform practice patterns and surgical treatment of patients presenting with compromised TKA and suggest that early involvement by reconstructive surgeons should be advocated to optimize reconstructive and functional outcomes in this difficult patient population.