IMPORTANCE Whether laminar airflow (LAF) in the operating room is effective for decreasing periprosthetic joint infection (PJI) after total joint arthroplasty remains a clinically important yet controversial issue. OBJECTIVE To investigate the association between operating room LAF ventilation systems and the risk of PJI in patients undergoing total joint arthroplasty. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted of 6972 consecutive patients undergoing primary total knee arthroplasty or total hip arthroplasty at 2 surgical facilities within a single institution from January 1, 2013, to September 15, 2017, with a minimum of 1 year of follow-up. All procedures were performed by 5 board-certified arthroplasty surgeons.