On March 6, 2017, the New Jersey Department of Health (NJDOH) was notified of three cases of septic arthritis in patients who had received intra-articular injections for osteoarthritic knee pain at a private outpatient practice. The practice voluntarily closed the next day. NJDOH, in conjunction with the local health department and the New Jersey Board of Medical Examiners, conducted an investigation and identified 41 cases of septic arthritis associated with intra-articular injections administered during 250 patient visits at the same practice, including 30 (73%) patients who required surgery. Bacterial cultures of synovial fluid or tissue from 15 (37%) patients were positive; all recovered organisms were oral flora. An infection prevention assessment of the practice identified multiple breaches of recommended infection prevention practices, including inadequate hand hygiene, inappropriate use of pharmacy bulk packaged (PBP) products as multiple-dose containers and handling PBP products outside of required pharmacy conditions, and preparation of syringes up to 4 days in advance of their intended use. No additional septic arthritis cases were identified after infection prevention recommendations were implemented within the practice.