Post-market clinical follow-up (PMCF) is a mandatory, ongoing process under EU MDR 2017/745, aimed at ensuring the continued safety and performance of medical devices. This manuscript outlines the regulatory requirements, methodologies, and integration of real-world data (RWD) in PMCF activities. It highlights how manufacturers can use RWD from registries, retrospective studies, and user surveys among other sources to fill clinical evidence gaps and support regulatory compliance. Case studies illustrate practical applications of RWD in PMCF. A systematic and data-driven PMCF approach is essential for effective post-market surveillance and the protection of patient health.