Background: Although calcific aortic valve disease (CAVD) is associated with coronary atherosclerosis, it is not known whether early CAVD is associated with coronary microcirculatory dysfunction (CMD). We sought to investigate the relationship between myocardial blood flow reserve (MBFR) - a measure of CMD, and early CAVD in the absence of obstructive epicardial coronary artery disease. We also determined whether this relationship was independent of coronary artery disease (CAD) and hs-CRP, a marker of systemic inflammation. Methods: 183 patients with chest pain and unobstructed coronary arteries were studied. Aortic valve calcification score (AVCS), coronary total plaque length (TPL), and coronary calcium score were quantified from multislice CT. MBFR was assessed using vasodilator myocardial contrast echocardiography. Hs-CRP was measured from venous blood using a particle-enhanced immunoassay. Results: Mean (± SD) participant age was 59.8 (9.6) years. Mean AVCS was 68 (258) AU, TPL was 15.6 (22.2) mm, and median coronary calcification score was 43.5 AU. Mean MBFR was 2.20 (0.52). Mean hs-CRP was 2.52 (3.86) mg/l. Multivariable linear regression modelling incorporating demographics, coronary plaque characteristics, MBFR, and inflammatory markers, demonstrated that age (β = 0.05, 95% CI: 0.02, 0.08, P = 0.007), hs-CRP (β = 0.09, CI: 0.02, 0.16, P = 0.010) and diabetes (β = 1.03, CI: 0.08, 1.98, P = 0.033), were positively associated with AVCS. MBFR (β = − 0.87, CI: − 1.44, − 0.30, P = 0.003), BMI (β = − 0.11, CI: − 0.21, − 0.01, P = 0.033), and LDL (β = − 0.32, CI: − 0.61, − 0.03, P = 0.029) were negatively associated with AVCS. TPL and coronary calcium score were not independently associated with AVCS when included in the regression model. Conclusion: Coronary microvascular function as determined by measurement of myocardial blood flow reserve is independently associated with early CAVD. This effect is independent of the presence of coronary artery disease and also systemic inflammation.