The total joint arthroplasty (TJA) is the most successful clinical surgical technique in the 20th century, and keeps increasing in number of cases. However, periprosthetic joint infection (PJI) is one of the most common and devastating complications after TJA, which mainly induced by Gram-positive bacteria, especially Staphylococcus aureus. Vancomycin may cover most of the pathogens causing PJI and plays an increasingly important role in the prevention of PJI with the increasing incidence of PJI caused by MRSA. The local administration of vancomycin to assist in the prevention of PJI is becoming more and more comprehensive with effectiveness and safety confirmed in animal experiments and/or retrospective trials, despite of lacking more robust evidence. Future studies should focus on large multicenter randomized trials to demonstrate effectiveness of vancomycin for PJI prevention further.