Administration of perioperative antibiotic prophylaxis (AP) reduces the risk of prosthetic joint infection (PJI) following primary total hip (THA) and knee (TKA) arthroplasty. The optimal type of antibiotic used, and duration of prophylaxis are subject to debate. We compared the risk of revision surgery for PJI in the first year following THA and TKA by AP regimen. A national survey collecting information on hospital-level AP regimen policy was conducted across the Netherlands and linked to data from the LROI arthroplasty registry for 2011–2015. PJI status was defined using the surgical indication reported at revision by surgeons in the registry form. Restricted cubic splines Poisson model adjusted for hospital clustering were used to conduct the comparisons on 130,712 THAs and 111,467 TKAs performed across 99 institutions. These included 399 THAs and 303 TKAs revised for an indication of PJI. Multiple shot of Cefazolin (MCZ), of cefuroxime (MCX) and single shot of Cefazolin (SCZ) were respectively administrated to 87%, 4% and 9% of patients. For THA, the rates of revision for PJI were respectively 31/10,000 person-years 95%CI[28, 35], 39[25, 59] and 23[15, 34] in the groups which received MCZ, MCX and SCZ; respectively, the rates for TKA were 27[24, 31], 40[24, 62] and 24[16, 36]. No evidence of difference between AP regimens was found in the unadjusted and adjusted model (age, gender, BMI and ASA grade). Further work is advocated to confirm whether there is an association between AP regimen collected at patient-level and the risk of subsequent revision for PJI.