Purpose: Patients with chest pain and unobstructed coronary arteries have an increased adverse cardiovascular outcome compared to those with normal coronary arteries. The aetiology is unclear but may be due to coronary microvascular dysfunction. In the largest study to date, we studied the relationship between risk factors (RF) for coronary disease (CD) and myocardial blood flow (MBF) in patients with chest pain and unobstructed coronary arteries. Methods: We recruited patients with chest pain and low or intermediate probability for CD, to undergo CT coronary angiography (CTCA). Those with either mild stenosis on CTCA or, moderate stenosis and normal functional imaging, had myocardial contrast echocardiography (MCE) at rest and during dipyridamole stress. MBF baseline (MBFb), stress (MBFs) and MBF reserve (MBFR) was obtained. High-sensitivity CRP (hs-CRP), arterial stiffness index (ASI) and carotid intima-media thickness (IMT) were measured. Results: 205 patients, mean age of 60±9.7 (range 32 – 81) years and 108 (53%) male were studied. Multiple regression analysis demonstrated the following to be significant independent predictors of reduction in MBF. Specifically, for each decade increase in age there was a 14% (p 6 RF. Between groups comparison indicated increasing RF was cumulatively associated with a reduction in MBFb: group A 32.5±7.0 dB2/s, group B 29.5±7.2 dB2/s, group C 26.6±6.0 dB2/s (p<0.01), and also MBFs: group A 69.8±13.7 dB2/s, group B 59.2±15.7 dB2/s, group C 52.0±14.7 dB2/s (p<0.001). There was no significant relationship with MBFR (group A 2.3±0.4, group B 2.2±0.5, group C 2.1±0.5). Conclusion: In patients with chest pain and unobstructed coronary arteries, MBF is significantly affected by risk factors for CAD. This effect is more pronounced as the number of risk factors increase.