Background: We aimed to evaluate the impact of knee periprosthetic joint infection (PJI) by assessing the patients' long-term quality of life and explicitly their psychological wellbeing after successful treatment. Methods: Thirty-six patients with achieved eradication of infection after knee PJI were included. Quality of life was evaluated with the EQ-5D and SF-36 outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data. Results: At a follow-up of 4.9 +/- 3.5 years the mean SF-36 score was 24.82 +/- 10.0 regarding the physical health component and 46.16 +/- 13.3 regarding the mental health component compared to German normative values of 48.36 +/- 9.4 (p < 0.001) and 50.87 +/- 8.8 (p = 0.003). The mean EQ-5D index reached 0.55 +/- 0.33 with an EQ-5D VAS rating of 52.14 +/- 19.9 compared to reference scores of 0.891 (p < 0.001) and 68.6 +/- 1.1 (p < 0.001). Mean scores of the ISR revealed the psychological symptom burden on the depression scale. Conclusion: PJI patients still suffer from significantly lower quality of life compared to normative data, even years after surgically successful treatment. Future clinical studies should focus on patient-related outcome measures. Newly emerging treatment strategies, prevention methods, and interdisciplinary approaches should be implemented to improve the quality of life of PJI patients.