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Abstract Healthcare-associated infections (HAIs) represent a relevant problem for all healthcare facilities, because they involve both the care aspect and the economic management of the hospital. Most HAIs are preventable through effective Infection Prevention and Control (IPC) measures. Implementation and improvement of IPC programs are critical to reducing the impact of these infections and the spread of multi-resistant microorganisms. The purpose of this Expert Opinion statement was to provide a practical guide for healthcare organizations, physicians, and nursing staff on the optimal implementation of the core components of Infection Prevention and Control, as recommended by a board of specialists after in-depth discussion of the available evidence in this field. According to their independent suggestions and clinical experiences, as well as evidence-based practices and literature review, this document provides a practical bundle of organizational, structural, and professional requirements necessary to promote, through multimodal strategies, the improvement of the quality and safety of care with respect to infectious risk in order to protect the patient, facilities, and healthcare providers.