Periprosthetic joint infection is one of the most challenging complications of joint arthroplasty. We identified current risk factors of periprosthetic joint infection after modern joint arthroplasty, and determined the incidence and timing of periprosthetic joint infection. We reviewed prospectively collected data from our database on 9245 patients undergoing primary hip or knee arthroplasty between January 2001 and April 2006. Periprosthetic joint infections developed in 63 patients (0.7%). Sixty-five percent of periprosthetic joint infections developed within the first year of the index arthroplasty. The infecting organism was isolated in 57 of 63 cases (91%). The most common organisms identified were Staphylococcus aureus and Staphylococcus epidermidis. We identified the following independent predictors for periprosthetic joint infection: higher American Society of Anesthesiologists score, morbid obesity, bilateral arthroplasty, knee arthroplasty, allogenic transfusion, postoperative atrial fibrillation, myocardial infarction, urinary tract infection, and longer hospitalization. This study confirmed some previously implicated factors and identified new variables that predispose patients to periprosthetic joint infection. Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. © 2008 The Association of Bone and Joint Surgeons.