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The aim of this document is to provide a set of indications on the national best practice management of knee osteoarthritis based on an analysis of the existing literature and the contribution of experts in the field. During the first phase of the project, in agreement with the multidisciplinary panel of experts, the main guidelines on the topic were selected. Each guideline was assessed through the AGREEII system to identify their strong/weak points and a summary of the recommendations contained in the various documents was drawn up. The panel drew up a list of therapeutic options to be included in the document and some of these topics were selected for in-depth analysis and review. The search strategy for the required literature reviews was constructed using the PICOS approach. The results obtained from the literature reviews, the in-depth analyses conducted by the members of the scientific societies involved and the analysis of the existing guidelines enabled an initial draft of the consensus document to be elaborated. This document was examined at the consensus conference held on 28 May 2019, in the presence of a multidisciplinary group consisting of members of the various scientific societies involved. Single recommendations were discussed in work groups with a view to combining the indications given by the literature examined with the experience of the specialists involved. The recommendations discussed were then put to the vote in a plenary assembly. The final document contains 26 practice recommendations which leading specialists involved in the management of knee OA in Italy agree upon., Competing Interests: G.A. Checchia has received consultancy fees and/or speaker honoraria from AlfaSigma AlfaWasserman outside this work; F. Franceschi declares no conflict of interest; L. Pradelli and T. Sinigaglia are employees of AdRes, which has been contracted by CDPharma, using an unconditional grant by Mylan for this work, and funding form many pharmaceutical and medical device companies outside this work; B. Frediani declares no conflict of interest; F. Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Lilly, Novartis, Sanofi, Celgene, UCB outside this work; E. Romanini declares no conflict of interest. The authors report no other conflicts of interest in this work., (© 2021 Pradelli et al.)