Aims. Periprosthetic joint infection (PJI) is a challenging complication of any arthroplasty procedure. We reviewed our use of static antibiotic-loaded cement spacers (ABLCSs) for staged management of PJI where segmental bone loss, ligamentous instability, or soft-tissue defects necessitate a static construct. We reviewed factors contributing to their failure and techniques to avoid these complications when using ABLCSs in this context. Methods. A retrospective analysis was conducted of 94 patients undergoing first-stage revision of an infected knee prosthesis between September 2007 and January 2020 at a single institution. Radiographs and clinical records were used to assess and classify the incidence and causes of static spacer failure. Of the 94 cases, there were 19 primary total knee arthroplasties (TKAs), ten revision TKAs (varus-valgus constraint), 20 hinged TKAs, one arthrodesis (nail), one failed spacer (performed elsewhere), 21 distal femoral endoprosthetic arthroplasties, and 22 proximal tibial arthroplasties. Results. A total of 35/94 patients (37.2%) had spacer-related complications, of which 26/35 complications (74.3%) were because of mechanical failure of the spacer construct, while 9/35 (25.7%) were due to recurrence of infection. Risk factors for internal failure were a construct where the total intramedullary spacer length was less than twice the length of the central osseous defect (p = 0.009), where proximal or distal intraosseous spacer contact was < 10%, and after tibial tubercle osteotomy (p = 0.005). The incidence of spacer complications significantly increased the time to second stage: mean 157 days (42 to 458) in those without complications versus 227 days (11 to 528) with complications (p = 0.014). Conclusion. The failure rate of static antibiotic-loaded cement spacers is much higher than anticipated. Complications of the spacer significantly increased the time to second-stage revision. The risk of mechanical failure is significantly increased if the spacer is less than double the size of the segmental defect, or if inadequate reinforcement is inserted into the residual bone. These findings serve as a guide for surgeons to avoid mechanical complications with static spacers. Cite this article: Bone Joint J 2024;106-B(10):1067–1073