BackgroundTwo-stage revision (TSR) knee arthroplasty is an established treatment, but failure to control infection still occurs in 4–50 % of cases. The aim of this study was to assess the infection eradication rate, risk factors for failure, and the clinical outcome after two-stage revision knee arthroplasty.MethodsThis retrospective study included 59 patients who had undergone at least one two-stage revision procedure due to periprosthetic joint infection (PJI). Demographic data, comorbidities, types of implant, and complications were analyzed. Univariate and multivariate logistic regression analysis were used to identify risk factors for failure.ResultsThe infections were controlled in 55 patients (93.2 %). The follow-up period was 4.1 (±2.7) years. Infection control was achieved after the first TSR in 42 patients (71.2 %) and after the second TSR in 13 (76.5 %). The percentage of arthrodesis procedures in patients with infection control increased from 16.75 % after one TSR to 69.2 % after two TSRs. Multivariate logistic regression analysis identified body mass index (BMI) (odds ratio 1.22; 95 % confidence intervals, 1.07 to 1.40; p = 0.004) and smoking (OR 21.52; 95 % CI, 2.60 to 178.19; p = 0.004) as risk factors for failure.ConclusionsTwo-stage revision protocols can achieve acceptable results even after a second procedure. It is still unclear whether the choice of implant influences failure rates. Risk factors for failure after two-stage revision were identified. Studies with larger sample sizes are needed in order to support these findings and identify further risk factors. To reduce failure rates, programs should be established to treat or minimize risk factors in patients with PJI.