Periprosthetic joint infections (PJIs) are fraught with multiple complications including poor patient-reported outcomes, disability, reinfection, disarticulation, and even death. We sought to perform a systematic review asking the question: (1) What is the mortality rate of a PJI of the knee undergoing 2-stage revision for infection? (2) Has this rate improved over time? (3) How does this compare to a normal cohort of individuals? We performed a database search in MEDLINE/EMBASE, PubMed, and all relevant reference studies using the following keywords: “periprosthetic joint infection,” “mortality rates,” “total knee arthroplasty,” and “outcomes after two stage revision.” Two hundred forty-two relevant studies and citations were identified, and 14 studies were extracted and included in the review. A total of 20,719 patients underwent 2-stage revision for total knee PJI. Average age was 66 years. Mean mortality percentage reported was 14.4% (1.7%-34.0%) with average follow-up 3.8 years (0.25-9 years). One-year mortality rate was 4.33% (3.14%-5.51%) after total knee PJI with an increase of 3.13% per year mortality thereafter (r = 0.76 0.49, 0.90, P < .001). Five-year mortality was 21.64%. When comparing the national age-adjusted mortality (Actuarial Life Table) and the reported 1-year mortality risk in this meta-analysis, the risk of death after total knee PJI is significantly increased, with an odds ratio of 3.05 (95% confidence interval, 2.69-3.44; P < .001). The mortality rate after 2-stage total knee revision for infection is very high. When counseling a patient regarding complications of this disease, death should be discussed.