IntroductionItaly represents one of major hubs for clinical research in Europe, nevertheless comprehensive long-term analyses of its clinical trial landscape under evolving regulatory frameworks remain limited. This study examines the trends of clinical trials submitted to the Italian Medicines Agency (AIFA) over a 10-year period, evaluating the impact of the COVID-19 pandemic, the transition to Regulation (EU) No. 536/2014 (CTR) and the introduction of the EU Clinical Trials Information System