Background: Clinical practice guidelines (CPGs) must be effectively implemented to result in meaningful improvements in patient care, support evidence-based decision-making, and drive high-quality, standardized medical practice.

Objectives: This paper is a guide to current best practices for quality implementation of CPGs, with a focus on the European Society of Clinical Microbiology and Infectious Diseases guidelines for the prevention, diagnosis, and management of infection.

Sources: The guide is informed by implementation science and based on the RE-AIM/PRISM implementation framework, one of the most used frameworks for planning and monitoring research-supported change in healthcare.

Content: A systematic approach to CPG implementation should be guided by three key principles commonly acknowledged in implementation science and reflected in the RE-AIM/PRISM model: (1) understanding the context into which the guideline will be embedded, (2) tailoring the guideline and its implementation to this context, and (3) monitoring guideline implementation.

Implications: To improve the applicability, effectiveness, and sustainability of novel CPGs, future advancements should prioritize their intentional, well-planned dissemination and implementation, and the rigorous evaluation of CPG outcomes.