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Background: Coronary microvascular dysfunction (CMD) is a prevalent condition among patients with cardiovascular risk factors, leading to a reduced quality of life and an increased risk of major adverse cardiovascular events. Novel invasive techniques have emerged to more accurately diagnose CMD. However, CMD's natural history remains poorly understood due to limited data. To address this knowledge gap, the Coronary Microvascular Disease Registry (CMDR) was established with the primary aim of standardizing comprehensive coronary functional testing and understanding of CMD., Design: CMDR is a prospective, multicenter registry enrolling an unlimited number of consecutive subjects who undergo comprehensive invasive hemodynamic assessment of the entire coronary arterial vasculature. Patients undergoing acetylcholine provocation test for coronary vasospasm will also be included. Follow-up assessments will be conducted at 30 days and annually for up to 5 years. The primary endpoint is Canadian Cardiovascular Society angina grade over time. Secondary endpoints, including all-cause mortality, cardiovascular death, acute myocardial infarction, stroke, hospitalizations, medication changes, and subsequent coronary interventions, will be analyzed to establish long-term safety and clinical outcomes in patients undergoing invasive CMD assessment., Summary: CMDR aims to characterize the clinical and physiologic profile of patients undergoing comprehensive invasive coronary functional testing, simultaneously providing crucial longitudinal information on the natural history and outcomes of these patients. This will shed light on CMD's course and clinical implications, which, in turn, holds the potential to significantly improve diagnostic and treatment strategies for CMD patients, ultimately leading to the enhancement of their overall prognosis and quality of life., Clinical Trial Registration: clinicaltrials.gov, NCT05960474., Competing Interests: Declaration of competing interest Brian C. Case, - Speaker: Asahi Intecc USA, Zoll Medical. Hector M. Garcia-Garcia – Institutional Grant Support: MedAlliance, Biotronik, Neovasc, Boston Scientific, Abbott, Shockwave, Chiesi, Philips, Spectrawave, Angiowave, InfraReDx, Medis, Pulse Medical, MedHub; Consultancy: Biotronik and Abbott; Speaker's fee: Abbott, Biotronik, Boston Scientific, InfraReDx. Hayder Hashim – Advisory Board, Speaker: Abbott Vascular, Boston Scientific, Philips IGT. Ron Waksman – Advisory Board: Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, Pi-Cardia Ltd.; Consultant: Abbott Vascular, Append Medical, Biotronik, Boston Scientific, JC Medical, MedAlliance/Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd., Swiss Interventional/SIS Medical AG, Transmural Systems Inc.; Institutional Grant Support: Biotronik, Medtronic, Philips IGT; Investor: Transmural Systems Inc. All other authors – None., (Copyright © 2024. Published by Elsevier Inc.)