Objective: This systematic review aimed to identify, synthesize, and critically analyze the available evidence on clinical protocols used for the prevention and treatment of prosthetic joint infection (PJI) in total hip arthroplasty (THA), based on studies published between 2000 and 2025. Methods: The review was conducted according to PRISMA guidelines. Electronic searches were performed in PubMed (MEDLINE), Scopus, Web of Science, and Embase between January and April 2025. Eligible studies included clinical trials, cohort studies, case-control studies, systematic reviews, and meta-analyses published in English that addressed either preventive or therapeutic strategies for PJI in THA. Study selection, data extraction, and quality assessment were carried out independently by two reviewers. Due to the heterogeneity of the included studies, a qualitative synthesis was performed. Results: A total of 32 studies were included. Preventive measures identified in the literature comprised combined antibiotic prophylaxis (cefazolin and gentamicin), multimodal perioperative protocols such as ACERTO, nasal decolonization for Staphylococcus aureus, silver-impregnated dressings, and structured post-discharge surveillance. Treatment strategies included DAIR (Debridement, Antibiotics, and Implant Retention), the DAPRI technique, one-stage and two-stage revision surgeries, muscle flap reconstructions, and protocols without spacers. These interventions were associated with significantly reduced infection rates and improved clinical outcomes when applied appropriately and in accordance with patient-specific factors. Conclusion: Effective prevention and treatment of PJI in total hip arthroplasty require a systematic and evidence-based approach. Integrated protocols—spanning preoperative optimization, meticulous intraoperative techniques, and rigorous postoperative monitoring—have proven effective in reducing infection incidence. In cases of established infection, surgical management must be tailored to the timing of infection, microbial profile, and host conditions. Two-stage revision remains the gold standard for complex infections, while one-stage revision and emerging techniques like DAPRI offer promising results in selected cases. This review contributes to the standardization of clinical practice and supports improved patient outcomes.Full article