Background <p>Total joint arthroplasty (TJA) has been increasingly performed in younger and medically complex patients. Ehlers–Danlos syndrome (EDS), a heritable connective tissue disorder characterised by ligamentous laxity and soft tissue fragility, may predispose patients to adverse arthroplasty outcomes, yet existing evidence remains fragmented.</p> Methods <p>A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. Comparative studies evaluating postoperative outcomes following primary TJA in patients with EDS versus non-EDS controls were identified from MEDLINE, Embase, Web of Science, and CENTRAL through November 2025. Random-effects meta-analyses were performed to estimate pooled risk ratios (RRs) for revision, instability or dislocation, aseptic loosening, periprosthetic fracture (PPFx), periprosthetic joint infection (PJI), wound complications, medical complications, and readmission or reoperation.</p> Results <p>Nine retrospective cohort studies encompassing over 415,000 patients were included. Compared with non-EDS patients, those with EDS demonstrated a significantly higher risk of instability or dislocation (RR 2.93, 95% CI 2.37–3.61) and all-cause revision (RR 1.97, 95% CI 1.29–3.02), particularly following total hip arthroplasty. Aseptic loosening and wound complications occurred more frequently in EDS patients, though associations were less consistent across models. No significant differences were observed in risks of PJI, medical complications, PPFx, or readmission or reoperation.</p> Conclusions <p>Patients with EDS undergoing TJA face substantially increased risks of mechanical complications, notably instability and revision, while infection and medical complication risks are comparable to those of non-EDS patients. These findings highlight the importance of targeted preoperative counselling and surgical strategies aimed at optimising joint stability in this high-risk population.</p>