Hamstring autograft use has been linked to an increased risk of infection after anterior cruciate (ACL) reconstruction compared to other grafts. The absolute reason for this remains unclear, with contamination after harvesting and preparation of the graft being the most accepted hypothesis. Using the rationale that a contaminated graft could be the main factor in postoperative septic arthritis and in an effort to maximize the antibiotic efficacy of the graft, the Vancomycin presoaking technique was developed. It has shown success in decreasing the infection rate in ACL reconstruction. In recent years, an important number of research articles using this protocol have appeared, but the technique is still not widely implemented. Recent literature shows that Vancomycin presoaking of the graft has shown a successful decrease in the infection rate after hamstring autograft ACL reconstruction. It has also shown efficacy decreasing the infection rate in other types of grafts (patellar tendon, quadriceps tendon, allograft) and also in patients with concomitant ligament procedures or open surgeries. Despite the positive effects of Vancomycin presoaking reducing the infection rate after ACL reconstruction, the lack of prospective randomized control trials and the heterogeneity of the different studies mean it is not feasible to recommend Vancomycin presoaking of the graft universally for every ACL reconstruction patient. Cite this article: EFORT Open Rev 2021;6:211-216. DOI: 10.1302/2058-5241.6.200059