Objectives: Periprosthetic joint infection (PJI) is an uncommon but serious complication following joint arthroplasty that results in significant patient morbidity, prolonged hospitalization, and substantial healthcare costs. While extensive literature addresses lower-limb arthroplasty, evidence for upper-limb procedures remains limited. This systematic review comprehensively examines prevention strategies across the preoperative, intraoperative, and postoperative phases for both upper- and lower-limb arthroplasties.

Methods: A systematic review following PRISMA 2020 guidelines was conducted. We searched PubMed, Scopus, Web of Science, and Cochrane Library databases for studies published from January 2003 to April 2026. Search terms included "prevention of periprosthetic joint infection," "joint replacement infection," and "periprosthetic joint infection." Two independent reviewers screened studies, extracted data using standardized forms, and assessed quality using Risk of Bias 2 (RoB2) for randomized controlled trials (RCTs), ROBINS-I for non-randomized controlled trials (NRCTs), and Newcastle-Ottawa Scale for observational studies. Narrative synthesis was performed due to study heterogeneity.

Results: Fifty-seven studies comprising 242,182 patients were included: 28 RCTs (49%), one NRCT (2%), 26 cohort studies (46%), and two case-control studies (4%). Lower limb arthroplasty was addressed in 45 studies (79%), upper limb in eight studies (14%), and both in four studies (7%). Quality assessment revealed 22 RCTs (79%) with low risk of bias, 20 cohort studies (77%) rated good quality, and both case-control studies rated good quality. Evidence synthesis identified fifteen evidence-based recommendations organized into five preoperative (medical optimization, bacterial decolonization, skin preparation, prophylactic antibiotics, and antibiotic-loaded bone cement), nine intraoperative (hair removal, draping, glove protocols, blood conservation, operation duration, operating room traffic, operating room environment, medical equipment, and wound closure), and one postoperative strategy (antibiotics and follow-up).

Conclusion: This systematic review represents the first comprehensive synthesis of PJI prevention strategies across the entire perioperative continuum. Implementation of these fifteen evidence-based recommendations can significantly reduce PJI incidence and improve outcomes in joint arthroplasties. Future research should prioritize RCTs examining combination strategies and upper limb-specific interventions.