Background <p>Posterior-stabilized cement articulating spacers (PS spacers) have superior knee scores and a greater range of motion in a two-stage exchange for chronic prosthetic knee infections (PKIs); however, mechanical complications are associated with the use of PS spacers. In the present study, we investigated a novel post-cam endoskeleton-reinforced PS spacer and its outcomes.</p> Methods <p>This single-surgeon retrospective cohort study included patients with chronic PKIs treated with PS spacers between 2015 and 2022. PS spacers with three different configurations, based on endoskeleton reinforcement, were compared: non-reinforced (n-PS), cam-reinforced alone (C-PS), and post- and cam-reinforced (PC-PS). Rates of mechanical complications, reoperation, and infection eradication were evaluated. The constraint choice of the revision prosthesis and risk factors for mechanical complications were analysed.</p> Results <p>In total, 186 patients, including 75 with n-PS, 61 with C-PS, and 50 with PC-PS spacers, were included. All patients were followed up for 2&#xa0;years. The rate of overall mechanical complications was lowest in patients treated with PC-PS spacers, particularly in patients with unstable joints after femoral cam and tibial post fracture and tibial spacer dislodgement. Moreover, neither spacer exchange nor rotating-hinge knee revision prosthesis was required in PC-PS spacers. Independent risk factors for mechanical complications were body mass index ≥ 25&#xa0;kg/m², femoral spacer size ≤ 2, and intra-operative maximum flexion ≥ 110°.</p> Conclusion <p>The novel PC-PS spacers prevented mechanical complications, spacer exchange, and the need for high-level constraint revision prostheses. We recommend the use of novel PC-PS spacers in two-stage exchange for chronic PKIs, especially in patients with a high body mass index, small femoral spacer size, and high knee flexion.</p>