A multidisciplinary panel of seven experts was convened by an independent organization, Avalere Health, to develop appropriate use criteria (AUC) for the use of hyaluronic acid (HA) injections for knee osteoarthritis (OA). The process for AUC development included a systematic review of 100 full-length articles that addressed one or more key questions and used the Delphi process to support the assessment of various clinical scenarios. Key questions used to guide the review addressed the effectiveness of HA versus placebo, the effectiveness of HA versus other therapies, the harms of HA use, the effectiveness of HA as a part of a multi-modal approach and the effectiveness of different HA doses and formulations.