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Background Failed total knee arthroplasty (TKA) with significant bone loss and compromised soft-tissues is challenging and the final results are often inferior to patient’s expectation. The objective of this study was to present a comparison of outcomes in patients with failed infected TKA treated with two-stage revision TKA or knee arthrodesis and to assess clinical and functional results, implant survival and infection recurrence. The hypothesis was that an arthrodesis may result in beneficial effects on patients’ outcome. Methods Clinical data of 81 patients with periprosthetic joint infection (PJI) of the knee joint were collected and analyzed retrospectively. Between 2008 and 2014, a total of 36 patients had been treated within a two-stage exchange procedure and reimplantation of a modular intramedullary arthodesis nail and 45 patients with revision TKA. Patients were treated according to the same structured treatment algorithm. Clinical and functional evaluation was performed using the Oxford knee score (OKS) and the visual analogue scale (VAS). Results The mean follow-up was 32.9 ± 14.0 months. The rate of definitely free of infection at last follow-up in the arthrodesis group was 32 of 36 (88.9%) and 36 of 45 (80.0%) in the revision TKA group (p = 0.272). Mean VAS for pain in the arthrodesis group was 3.1 ± 1.4 compared to 3.2 ± 1.6 in the revision TKA group (p = 0.636). The OKS in the arthrodesis group was 38.7 ± 8.9 and 36.5 ± 8.9 (p = 0.246) in patients with revision TKA. Rate of revisions in the revision-TKA group was 2.8 ± 3.7 compared to 1.2 ± 2.4 in the arthrodesis group (p = 0.021). Conclusion Treatment of PJI needs a distinct therapy with possible fallback strategies in case of failure. A knee arthrodesis is a limb salvage procedure that showed no significant benefits on the considered outcome factors compared to revision TKA but is associated with significantly lower revision rate. After exhausted treatment modalities, a knee arthrodesis should be considered as an option in selected patients.